NM_001144060.2:c.212-4885C>T

Variant names:

• chr6-138478318-G-A
• rs10499202
• NM_001144060.2:c.212-4885C>T

Variant summary

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

The NM_001144060.2(NHSL1):​c.212-4885C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,832 control chromosomes in the GnomAD database, including 3,999 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 0.22 (3999 hom., cov: 31)
• Consequence: NHSL1 NM_001144060.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHSL1	NM_001144060.2	c.212-4885C>T		intron_variant	Intron 2 of 7	ENST00000343505.10	NP_001137532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHSL1	ENST00000343505.10	c.212-4885C>T		intron_variant	Intron 2 of 7	5	NM_001144060.2	ENSP00000344672.5

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33439 AN: 151714 Hom.: 3984 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.221 AC: 33488 AN: 151832 Hom.: 3999 Cov.: 31 AF XY: 0.217 AC XY: 16097 AN XY: 74208

African (AFR) AF: 0.226 AC: 9369 AN: 41394

American (AMR) AF: 0.350 AC: 5323 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3466

East Asian (EAS) AF: 0.355 AC: 1828 AN: 5144

South Asian (SAS) AF: 0.159 AC: 766 AN: 4812

European-Finnish (FIN) AF: 0.114 AC: 1198 AN: 10536

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.200 AC: 13572 AN: 67944

Other (OTH) AF: 0.251 AC: 530 AN: 2108

Alfa AF: 0.178 Hom.: 1211

Bravo AF: 0.241

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.73
PhyloP100		-1.6
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: rs10499202; hg19: chr6-138799455;