Genetic Variant NHSL1:p.Gly1494Gly (chr6-138424420-G-C) – ACMG Classification: Benign (-15 pts)

Variant summary

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

The NM_001144060.2(NHSL1):c.4482C>G(p.Gly1494Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,550,188 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0079 ( 15 hom., cov: 31)

Exomes 𝑓: 0.00090 ( 10 hom. )

Consequence

NHSL1
NM_001144060.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.606

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=-0.76).

BP6

Variant 6-138424420-G-C is Benign according to our data. Variant chr6-138424420-G-C is described in ClinVar as [Benign]. Clinvar id is 710994.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.606 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00786 (1197/152216) while in subpopulation AFR AF= 0.0277 (1150/41542). AF 95% confidence interval is 0.0264. There are 15 homozygotes in gnomad4. There are 557 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHSL1	NM_001144060.2 link	c.4482C>G	p.Gly1494Gly	synonymous_variant	Exon 8 of 8	ENST00000343505.10	NP_001137532.1	Q5SYE7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHSL1	ENST00000343505.10 link	c.4482C>G	p.Gly1494Gly	synonymous_variant	Exon 8 of 8	5	NM_001144060.2	ENSP00000344672.5		Q5SYE7-2
NHSL1	ENST00000427025.6 link	c.4494C>G	p.Gly1498Gly	synonymous_variant	Exon 7 of 7	5		ENSP00000394546.2		Q5SYE7-1

Frequencies

GnomAD3 genomes

AF:

0.00786

AC:

1195

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

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:

0.0000441

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00157

AC:

242

AN:

153826

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

81624

show subpopulations

Gnomad AFR exome

AF:

0.0263

Gnomad AMR exome

AF:

0.000893

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000879

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000839

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000900

AC:

1258

AN:

1397972

Hom.:

Cov.:

AF XY:

0.000782

AC XY:

539

AN XY:

689268

show subpopulations

Gnomad4 AFR exome

AF:

0.0306

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.00786

AC:

1197

AN:

152216

Hom.:

Cov.:

AF XY:

0.00748

AC XY:

557

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00888

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 15, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.6

DANN

Benign

0.71

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