Genetic Variant NEUROG1:p.Pro156Pro (chr5-135535223-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006161.3(NEUROG1):c.468C>T(p.Pro156Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,612,210 control chromosomes in the GnomAD database, including 6,444 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.067 ( 512 hom., cov: 33)

Exomes 𝑓: 0.085 ( 5932 hom. )

Consequence

NEUROG1
NM_006161.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.762

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=0.762 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.096 is higher than 0.05.

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.468C>T	p.Pro156Pro	synonymous	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.468C>T	p.Pro156Pro	synonymous	Exon 1 of 1	ENSP00000317580.4	Q92886
ENSG00000250167	ENST00000698884.1		n.496+48454G>A		intron	N/A
SLC25A48	ENST00000698885.1		n.364+25467G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

10183

AN:

152140

Hom.:

513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0894

Gnomad ASJ

AF:

0.0536

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0165

Gnomad FIN

AF:

0.0953

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0980

Gnomad OTH

AF:

0.0559

GnomAD2 exomes

AF:

0.0689

AC:

16783

AN:

243628

AF XY:

0.0680

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.0720

Gnomad ASJ exome

AF:

0.0541

Gnomad EAS exome

AF:

0.000277

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0951

Gnomad OTH exome

AF:

0.0747

GnomAD4 exome

AF:

0.0852

AC:

124367

AN:

1459960

Hom.:

5932

Cov.:

AF XY:

0.0833

AC XY:

60531

AN XY:

726322

show subpopulations

African (AFR)

AF:

0.0137

AC:

456

AN:

33404

American (AMR)

AF:

0.0722

AC:

3226

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.0547

AC:

1426

AN:

26074

East Asian (EAS)

AF:

0.000177

AC:

AN:

39642

South Asian (SAS)

AF:

0.0182

AC:

1573

AN:

86210

European-Finnish (FIN)

AF:

0.103

AC:

5411

AN:

52608

Middle Eastern (MID)

AF:

0.0222

AC:

127

AN:

5728

European-Non Finnish (NFE)

AF:

0.0970

AC:

107778

AN:

1111358

Other (OTH)

AF:

0.0724

AC:

4363

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

7430

14860

22291

29721

37151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3782

7564

11346

15128

18910

<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:

0.0669

AC:

10178

AN:

152250

Hom.:

512

Cov.:

AF XY:

0.0654

AC XY:

4866

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0164

AC:

681

AN:

41570

American (AMR)

AF:

0.0890

AC:

1362

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0536

AC:

186

AN:

3468

East Asian (EAS)

AF:

0.000388

AC:

AN:

5158

South Asian (SAS)

AF:

0.0172

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0953

AC:

1011

AN:

10614

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0980

AC:

6661

AN:

67994

Other (OTH)

AF:

0.0553

AC:

117

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

475

950

1425

1900

2375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0745

Hom.:

361

Bravo

AF:

0.0629

Asia WGS

AF:

0.0130

AC:

AN:

3472

EpiCase

AF:

0.0858

EpiControl

AF:

0.0887

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.6

(source)

DANN

Benign

0.89

PhyloP100

0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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