rs10499199

Positions:

• chr6-138448709-A-C
• chr6-138448709-A-G

Variant summary

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

The NM_001144060.2(NHSL1):​c.340-1516T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,304 control chromosomes in the GnomAD database, including 1,128 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 0.12 (1128 hom., cov: 33)
• Consequence: NHSL1 NM_001144060.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) 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.340-1516T>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.340-1516T>G		intron_variant		5	NM_001144060.2	ENSP00000344672	P3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17724 AN: 152186 Hom.: 1128 Cov.: 33

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.116 AC: 17732 AN: 152304 Hom.: 1128 Cov.: 33 AF XY: 0.110 AC XY: 8181 AN XY: 74468

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0827

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.140

Alfa AF: 0.0751 Hom.: 96

Bravo AF: 0.119

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.72

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: rs10499199; hg19: chr6-138769846;