Variant 3-149041582-T-C 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_003071.4(HLTF):c.2284A>G(p.Ile762Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,612,468 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 30 hom. )

Consequence

HLTF
NM_003071.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.61

Variant links:

Genes affected

HLTF (HGNC:11099): (helicase like transcription factor) This gene encodes a member of the SWI/SNF family. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein contains a RING finger DNA binding motif. Two transcript variants encoding the same protein have been found for this gene. However, use of an alternative translation start site produces an isoform that is truncated at the N-terminus compared to the full-length protein. [provided by RefSeq, Jul 2008]

HLTF 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 (MetaRNN=0.005889535).

BP6

Variant 3-149041582-T-C is Benign according to our data. Variant chr3-149041582-T-C is described in ClinVar as [Benign]. Clinvar id is 787259.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1750/152238) while in subpopulation AFR AF= 0.0404 (1678/41562). AF 95% confidence interval is 0.0388. There are 37 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLTF	NM_003071.4 linkuse as main transcript	c.2284A>G	p.Ile762Val	missense_variant	20/25	ENST00000310053.10	NP_003062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLTF	ENST00000310053.10 linkuse as main transcript	c.2284A>G	p.Ile762Val	missense_variant	20/25	1	NM_003071.4	ENSP00000308944	P4	Q14527-1

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1749

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

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:

0.000103

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00299

AC:

751

AN:

251188

Hom.:

AF XY:

0.00220

AC XY:

299

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0405

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00124

AC:

1808

AN:

1460230

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

737

AN XY:

726544

show subpopulations

Gnomad4 AFR exome

AF:

0.0449

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.00254

GnomAD4 genome

AF:

0.0115

AC:

1750

AN:

152238

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

842

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0404

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00550

Hom.:

Bravo

AF:

0.0131

ESP6500AA

AF:

0.0399

AC:

176

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00351

AC:

426

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

.;T;T;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.85

D;.;.;D;D

MetaRNN

Benign

0.0059

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L;L;L;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.56

N;N;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.20

T;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;.

Polyphen

0.0040

.;B;B;B;.

Vest4

0.094

MVP

0.60

MPC

0.16

ClinPred

0.0065

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.25

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