rs6926204

Positions:

• chr6-138457223-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144060.2(NHSL1):​c.340-10030A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,232 control chromosomes in the GnomAD database, including 1,436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1436 hom., cov: 32)
• Consequence: NHSL1 NM_001144060.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHSL1	NM_001144060.2	c.340-10030A>G		intron_variant		ENST00000343505.10	NP_001137532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHSL1	ENST00000343505.10	c.340-10030A>G		intron_variant		5	NM_001144060.2	ENSP00000344672	P3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20671 AN: 152114 Hom.: 1433 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20693 AN: 152232 Hom.: 1436 Cov.: 32 AF XY: 0.129 AC XY: 9585 AN XY: 74436

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0814

Gnomad4 FIN AF: 0.0666

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.153

Alfa AF: 0.137 Hom.: 174

Bravo AF: 0.142

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs6926204; hg19: chr6-138778360;