rs4895529

Positions:

• chr6-138449138-C-G

Variant summary

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

The NM_001144060.2(NHSL1):​c.340-1945G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 151,672 control chromosomes in the GnomAD database, including 784 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 0.063 (784 hom., cov: 32)
• Consequence: NHSL1 NM_001144060.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHSL1	NM_001144060.2	c.340-1945G>C		intron_variant		ENST00000343505.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHSL1	ENST00000343505.10	c.340-1945G>C		intron_variant		5	NM_001144060.2	P3

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9461 AN: 151586 Hom.: 773 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0413

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0543

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

GnomAD4 genome AF: 0.0625 AC: 9483 AN: 151672 Hom.: 784 Cov.: 32 AF XY: 0.0697 AC XY: 5161 AN XY: 74066

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.0413

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.0741

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0398

Gnomad4 OTH AF: 0.0571

Alfa AF: 0.0497 Hom.: 45

Bravo AF: 0.0686

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.56

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: rs4895529; hg19: chr6-138770275;