5-135535590-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006161.3(NEUROG1):c.101G>A(p.Arg34Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,591,594 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 7 hom. )

Consequence

NEUROG1
NM_006161.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.94

Publications

2 publications found

Variant links:

Genes affected

NEUROG1 (HGNC:7764): (neurogenin 1) Enables E-box binding activity and protein homodimerization activity. Involved in several processes, including animal organ morphogenesis; cranial nerve development; and hard palate morphogenesis. Predicted to be located in neuronal cell body. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NEUROG1 links:

ENSG00000250167 (HGNC:):

ENSG00000250167 links:

SLC25A48 (HGNC:30451): (solute carrier family 25 member 48) Predicted to enable acyl carnitine transmembrane transporter activity. Predicted to be involved in acyl carnitine transport and amino acid transport. Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC25A48 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066720843).

BP6

Variant 5-135535590-C-T is Benign according to our data. Variant chr5-135535590-C-T is described in ClinVar as Benign. ClinVar VariationId is 712449.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00531 (809/152332) while in subpopulation AFR AF = 0.0185 (769/41586). AF 95% confidence interval is 0.0174. There are 16 homozygotes in GnomAd4. There are 383 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006161.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEUROG1	NM_006161.3	MANE Select	c.101G>A	p.Arg34Lys	missense	Exon 1 of 1	NP_006152.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEUROG1	ENST00000314744.6	TSL:6 MANE Select	c.101G>A	p.Arg34Lys	missense	Exon 1 of 1	ENSP00000317580.4	Q92886
ENSG00000250167	ENST00000698884.1		n.496+48821C>T		intron	N/A
SLC25A48	ENST00000698885.1		n.364+25834C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00529

AC:

805

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00130

AC:

277

AN:

213192

AF XY:

0.00102

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000309

Gnomad OTH exome

AF:

0.000372

GnomAD4 exome

AF:

0.000560

AC:

806

AN:

1439262

Hom.:

Cov.:

AF XY:

0.000499

AC XY:

357

AN XY:

715616

show subpopulations

African (AFR)

AF:

0.0203

AC:

657

AN:

32326

American (AMR)

AF:

0.000979

AC:

AN:

42886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25616

East Asian (EAS)

AF:

0.00

AC:

AN:

38716

South Asian (SAS)

AF:

0.0000477

AC:

AN:

83864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43202

Middle Eastern (MID)

AF:

0.000697

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

1107152

Other (OTH)

AF:

0.00137

AC:

AN:

59758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

135

180

225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00531

AC:

809

AN:

152332

Hom.:

Cov.:

AF XY:

0.00514

AC XY:

383

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0185

AC:

769

AN:

41586

American (AMR)

AF:

0.00196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

117

156

195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00200

Hom.:

Bravo

AF:

0.00624

ESP6500AA

AF:

0.0149

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00168

AC:

201

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.27

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.42

MutationAssessor

Benign

1.8

PhyloP100

2.9

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.0

REVEL

Benign

0.27

Sift

Benign

0.15

Sift4G

Benign

0.86

Polyphen

0.61

Vest4

0.047

MVP

0.82

MPC

0.49

ClinPred

0.012

GERP RS

3.8

PromoterAI

0.0072

Neutral

(source)

Varity_R

0.088

gMVP

0.26

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over