Variant 17-74748772-G-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.-75G>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 0.0271 in 1,335,408 control chromosomes in the GnomAD database, including 638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.021 ( 49 hom., cov: 33)

Exomes 𝑓: 0.028 ( 589 hom. )

Consequence

NHERF1
NM_004252.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.497

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:

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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 17-74748772-G-A is Benign according to our data. Variant chr17-74748772-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1315840.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-74748772-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.021 (3201/152254) while in subpopulation NFE AF= 0.0323 (2197/67990). AF 95% confidence interval is 0.0312. There are 49 homozygotes in gnomad4. There are 1480 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3201 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHERF1	NM_004252.5 linkuse as main transcript	c.-75G>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.-75G>A	5_prime_UTR_variant	1/6	1	NM_004252.5	P1	O14745-1
SLC9A3R1-AS1	ENST00000585285.1 linkuse as main transcript	n.141C>T	non_coding_transcript_exon_variant	1/2	3
NHERF1	ENST00000583369.5 linkuse as main transcript	c.-75G>A	5_prime_UTR_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3202

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00591

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00942

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.0210

GnomAD4 exome

AF:

0.0279

AC:

32978

AN:

1183154

Hom.:

589

Cov.:

AF XY:

0.0275

AC XY:

16148

AN XY:

587336

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.0174

Gnomad4 ASJ exome

AF:

0.0566

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00789

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.0315

Gnomad4 OTH exome

AF:

0.0265

GnomAD4 genome

AF:

0.0210

AC:

3201

AN:

152254

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1480

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00589

Gnomad4 AMR

AF:

0.0246

Gnomad4 ASJ

AF:

0.0550

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.00942

Gnomad4 NFE

AF:

0.0323

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0235

Hom.:

Bravo

AF:

0.0215

Asia WGS

AF:

0.00260

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

Sep 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.2

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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