dbSNP rs4618: NREP:c.*1190A>C (chr5-111729731-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004772.4(NREP):c.*1190A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,520 control chromosomes in the GnomAD database, including 11,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.34 ( 11838 hom., cov: 33)

Exomes 𝑓: 0.18 ( 6 hom. )

Consequence

NREP
NM_004772.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.44

Publications

11 publications found

Variant links:

Genes affected

NREP (HGNC:16834): (neuronal regeneration related protein) Predicted to be involved in axon regeneration; regulation of neuron differentiation; and regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NREP links:

STARD4-AS1 (HGNC:44117): (STARD4 antisense RNA 1)

STARD4-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004772.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NREP	NM_004772.4	MANE Select	c.*1190A>C	3_prime_UTR	Exon 4 of 4	NP_004763.1	Q16612-1
NREP	NM_001142475.2		c.*1190A>C	3_prime_UTR	Exon 4 of 4	NP_001135947.1	Q16612-2
NREP	NM_001142474.2		c.*1190A>C	3_prime_UTR	Exon 4 of 4	NP_001135946.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NREP	ENST00000257435.12	TSL:1 MANE Select	c.*1190A>C	3_prime_UTR	Exon 4 of 4	ENSP00000257435.7	Q16612-1
NREP	ENST00000379671.7	TSL:1	c.*1190A>C	3_prime_UTR	Exon 5 of 5	ENSP00000368993.3	Q16612-1
NREP	ENST00000447165.6	TSL:1	c.*1190A>C	3_prime_UTR	Exon 3 of 3	ENSP00000408839.2	Q16612-1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52294

AN:

151974

Hom.:

11809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.323

GnomAD4 exome

AF:

0.180

AC:

AN:

428

Hom.:

Cov.:

AF XY:

0.202

AC XY:

AN XY:

258

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.175

AC:

AN:

418

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.344

AC:

52364

AN:

152092

Hom.:

11838

Cov.:

AF XY:

0.339

AC XY:

25214

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.650

AC:

26924

AN:

41450

American (AMR)

AF:

0.310

AC:

4742

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

664

AN:

3472

East Asian (EAS)

AF:

0.330

AC:

1702

AN:

5162

South Asian (SAS)

AF:

0.164

AC:

791

AN:

4818

European-Finnish (FIN)

AF:

0.177

AC:

1879

AN:

10602

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14756

AN:

67994

Other (OTH)

AF:

0.322

AC:

680

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1519

3038

4557

6076

7595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.109

Hom.:

159

Bravo

AF:

0.371

Asia WGS

AF:

0.265

AC:

923

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

2.4

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over