Variant chr17-74748731-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004252.5(NHERF1):c.-116C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 926,672 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

NHERF1
NM_004252.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.875

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:):

SLC9A3R1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 17-74748731-C-T is Benign according to our data. Variant chr17-74748731-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2572959.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 445 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
NHERF1	NM_004252.5 linkuse as main transcript	c.-116C>T	5_prime_UTR_variant	1/6	ENST00000262613.10	NP_004243.1	O14745-1
SLC9A3R1-AS1	NR_187307.1 linkuse as main transcript	n.1002G>A	non_coding_transcript_exon_variant	2/3
MIR3615	NR_037409.1 linkuse as main transcript	n.*32C>T	downstream_gene_variant
MIR3615	unassigned_transcript_3092 use as main transcript	n.*48C>T	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NHERF1	ENST00000262613.10 linkuse as main transcript	c.-116C>T	5_prime_UTR_variant	1/6	1	NM_004252.5	ENSP00000262613.5	O14745-1
NHERF1	ENST00000583369.5 linkuse as main transcript	c.-116C>T	5_prime_UTR_variant	1/3	3		ENSP00000464321.1	J3QRP6
SLC9A3R1-AS1	ENST00000585285.1 linkuse as main transcript	n.182G>A	non_coding_transcript_exon_variant	1/2	3
MIR3615	ENST00000581999.1 linkuse as main transcript	n.*32C>T	downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

439

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00999

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000612

AC:

AN:

60460

Hom.:

AF XY:

0.000425

AC XY:

AN XY:

32918

show subpopulations

Gnomad AFR exome

AF:

0.00939

Gnomad AMR exome

AF:

0.000355

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000256

AC:

198

AN:

774390

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

392218

show subpopulations

Gnomad4 AFR exome

AF:

0.00807

Gnomad4 AMR exome

AF:

0.000829

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000213

Gnomad4 OTH exome

AF:

0.000760

GnomAD4 genome

AF:

0.00292

AC:

445

AN:

152282

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00342

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

May 25, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.2

DANN

Benign

0.87

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