NM_001144060.2:c.532+1126T>C

Variant names:

• chr6-138445875-A-G
• rs17067596
• NM_001144060.2:c.532+1126T>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.532+1126T>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 152,252 control chromosomes in the GnomAD database, including 796 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 (796 hom., cov: 32)
• Consequence: NHSL1 NM_001144060.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144060.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHSL1	NM_001144060.2	MANE Select	c.532+1126T>C		intron	N/A	NP_001137532.1	Q5SYE7-2
	NHSL1	NM_020464.2		c.676+1126T>C		intron	N/A	NP_065197.1	Q5SYE7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHSL1	ENST00000343505.10	TSL:5 MANE Select	c.532+1126T>C		intron	N/A	ENSP00000344672.5	Q5SYE7-2
	NHSL1	ENST00000491526.7	TSL:3	c.763+1126T>C		intron	N/A	ENSP00000433523.2	H0YDF6
	NHSL1	ENST00000427025.6	TSL:5	c.676+1126T>C		intron	N/A	ENSP00000394546.2	Q5SYE7-1

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9497 AN: 152134 Hom.: 785 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0540

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

GnomAD4 genome AF: 0.0625 AC: 9519 AN: 152252 Hom.: 796 Cov.: 32 AF XY: 0.0697 AC XY: 5190 AN XY: 74440

African (AFR) AF: 0.0109 AC: 452 AN: 41556

American (AMR) AF: 0.181 AC: 2761 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1875 AN: 5176

South Asian (SAS) AF: 0.0737 AC: 356 AN: 4828

European-Finnish (FIN) AF: 0.101 AC: 1065 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0399 AC: 2713 AN: 68012

Other (OTH) AF: 0.0567 AC: 120 AN: 2116

Alfa AF: 0.0637 Hom.: 112

Bravo AF: 0.0685

Asia WGS AF: 0.211 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.62
PhyloP100		-0.27
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: rs17067596; hg19: chr6-138767012;