rs6910844

Positions:

• chr6-138561714-T-C

Variant summary

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

The NM_020464.2(NHSL1):​c.202+9996A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,022 control chromosomes in the GnomAD database, including 12,284 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 0.32 (12284 hom., cov: 32)
• Consequence: NHSL1 NM_020464.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHSL1	NM_020464.2	c.202+9996A>G		intron_variant			NP_065197.1
NHSL1	XM_011535976.2	c.290-65343A>G		intron_variant			XP_011534278.2
NHSL1	XM_047419109.1	c.290-65343A>G		intron_variant			XP_047275065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHSL1	ENST00000427025.6	c.202+9996A>G		intron_variant		5		ENSP00000394546.2
NHSL1	ENST00000491526.6	c.95-65343A>G		intron_variant		3		ENSP00000433523.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49205 AN: 151904 Hom.: 12231 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.324 AC: 49314 AN: 152022 Hom.: 12284 Cov.: 32 AF XY: 0.323 AC XY: 23961 AN XY: 74288

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.308

Alfa AF: 0.202 Hom.: 2217

Bravo AF: 0.347

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6910844; hg19: chr6-138882851;