Variant 6-138424771-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001144060.2(NHSL1):c.4131C>T(p.His1377=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,551,402 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 36 hom. )

Consequence

NHSL1
NM_001144060.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.525

Variant links:

Genes affected

NHSL1 (HGNC:21021): (NHS like 1) Predicted to be involved in cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

NHSL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 6-138424771-G-A is Benign according to our data. Variant chr6-138424771-G-A is described in ClinVar as [Benign]. Clinvar id is 781757.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.525 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00272 (414/152230) while in subpopulation AMR AF= 0.0193 (295/15300). AF 95% confidence interval is 0.0175. There are 5 homozygotes in gnomad4. There are 197 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHSL1	NM_001144060.2 linkuse as main transcript	c.4131C>T	p.His1377=	synonymous_variant	8/8	ENST00000343505.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHSL1	ENST00000343505.10 linkuse as main transcript	c.4131C>T	p.His1377=	synonymous_variant	8/8	5	NM_001144060.2	P3	Q5SYE7-2
NHSL1	ENST00000427025.6 linkuse as main transcript	c.4143C>T	p.His1381=	synonymous_variant	7/7	5		A2	Q5SYE7-1

Frequencies

GnomAD3 genomes

AF:

0.00266

AC:

405

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00626

AC:

973

AN:

155426

Hom.:

AF XY:

0.00492

AC XY:

405

AN XY:

82394

show subpopulations

Gnomad AFR exome

AF:

0.000634

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.00119

Gnomad SAS exome

AF:

0.00264

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00572

GnomAD4 exome

AF:

0.00136

AC:

1899

AN:

1399172

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

884

AN XY:

690114

show subpopulations

Gnomad4 AFR exome

AF:

0.000475

Gnomad4 AMR exome

AF:

0.0338

Gnomad4 ASJ exome

AF:

0.00155

Gnomad4 EAS exome

AF:

0.00104

Gnomad4 SAS exome

AF:

0.00220

Gnomad4 FIN exome

AF:

0.00171

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.00321

GnomAD4 genome

AF:

0.00272

AC:

414

AN:

152230

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

197

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.0193

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00329

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00477

Asia WGS

AF:

0.0200

AC:

AN:

3478

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.5

DANN

Benign

0.63

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