chr6-138450815-A-G

Variant names:

• chr6-138450815-A-G
• rs10499200
• NM_001144060.2:c.340-3622T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144060.2(NHSL1):​c.340-3622T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,170 control chromosomes in the GnomAD database, including 1,335 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 0.13 (1335 hom., cov: 32)
• Consequence: NHSL1 NM_001144060.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• 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 rank	MANE	Protein	UniProt
NHSL1	NM_001144060.2	c.340-3622T>C		intron_variant	Intron 3 of 7	ENST00000343505.10	NP_001137532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHSL1	ENST00000343505.10	c.340-3622T>C		intron_variant	Intron 3 of 7	5	NM_001144060.2	ENSP00000344672.5

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19913 AN: 152052 Hom.: 1332 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.131 AC: 19933 AN: 152170 Hom.: 1335 Cov.: 32 AF XY: 0.124 AC XY: 9239 AN XY: 74406

African (AFR) AF: 0.137 AC: 5669 AN: 41520

American (AMR) AF: 0.125 AC: 1904 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3464

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5178

South Asian (SAS) AF: 0.0827 AC: 399 AN: 4822

European-Finnish (FIN) AF: 0.0666 AC: 705 AN: 10584

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10283 AN: 68006

Other (OTH) AF: 0.149 AC: 314 AN: 2110

Alfa AF: 0.147 Hom.: 5407

Bravo AF: 0.136

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.63
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10499200; hg19: chr6-138771952;