Variant chr17-74748804-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004252.5(NHERF1):c.-43C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,531,540 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0079 ( 10 hom., cov: 33)

Exomes 𝑓: 0.014 ( 180 hom. )

Consequence

NHERF1
NM_004252.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.204

Variant links:

Genes affected

NHERF1 (HGNC:11075): (NHERF family PDZ scaffold protein 1) This gene encodes a sodium/hydrogen exchanger regulatory cofactor. The protein interacts with and regulates various proteins including the cystic fibrosis transmembrane conductance regulator and G-protein coupled receptors such as the beta2-adrenergic receptor and the parathyroid hormone 1 receptor. The protein also interacts with proteins that function as linkers between integral membrane and cytoskeletal proteins. The protein localizes to actin-rich structures including membrane ruffles, microvilli, and filopodia. Mutations in this gene result in hypophosphatemic nephrolithiasis/osteoporosis type 2, and loss of heterozygosity of this gene is implicated in breast cancer.[provided by RefSeq, Sep 2009]

NHERF1 links:

SLC9A3R1-AS1 (HGNC:55322): (SLC9A3R1 antisense RNA 1)

SLC9A3R1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 17-74748804-C-A is Benign according to our data. Variant chr17-74748804-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316123.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00787 (1198/152272) while in subpopulation SAS AF= 0.0188 (91/4830). AF 95% confidence interval is 0.0157. There are 10 homozygotes in gnomad4. There are 542 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1198 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHERF1	NM_004252.5 linkuse as main transcript	c.-43C>A		5_prime_UTR_variant	1/6	ENST00000262613.10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHERF1	ENST00000262613.10 linkuse as main transcript	c.-43C>A	5_prime_UTR_variant	1/6	1	NM_004252.5	P1	O14745-1
SLC9A3R1-AS1	ENST00000585285.1 linkuse as main transcript	n.109G>T	non_coding_transcript_exon_variant	1/2	3
NHERF1	ENST00000583369.5 linkuse as main transcript	c.-43C>A	5_prime_UTR_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.00787

AC:

1197

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0186

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.0104

AC:

1712

AN:

164426

Hom.:

AF XY:

0.0115

AC XY:

1046

AN XY:

91072

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.00574

Gnomad ASJ exome

AF:

0.00524

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0197

Gnomad FIN exome

AF:

0.00247

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.00881

GnomAD4 exome

AF:

0.0144

AC:

19909

AN:

1379268

Hom.:

180

Cov.:

AF XY:

0.0147

AC XY:

10070

AN XY:

684374

show subpopulations

Gnomad4 AFR exome

AF:

0.00223

Gnomad4 AMR exome

AF:

0.00591

Gnomad4 ASJ exome

AF:

0.00629

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.00307

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00787

AC:

1198

AN:

152272

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

542

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00255

Gnomad4 AMR

AF:

0.00483

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0188

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00864

Hom.:

Bravo

AF:

0.00779

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.2

DANN

Benign

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over