rs41557518

Variant names:

• chr6-29828657-AC-A
• rs41557518
• NM_001384290.1:c.460delC

Your query was ambiguous. Multiple possible variants found:

• chr6-29828657-AC-A
• chr6-29828657-AC-ACC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384290.1(HLA-G):​c.460delC​(p.Leu154CysfsTer60) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,460 control chromosomes in the GnomAD database, including 347 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.028 (101 hom., cov: 32)
  • Exomes 𝑓: 0.013 (246 hom.)
• Consequence: HLA-G NM_001384290.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 16 publications found

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384290.1. 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
	HLA-G	NM_001384290.1	MANE Select	c.460delC	p.Leu154CysfsTer60	frameshift	Exon 3 of 7	NP_001371219.1	Q6DU14
	HLA-G	NM_001363567.2		c.475delC	p.Leu159CysfsTer60	frameshift	Exon 4 of 8	NP_001350496.1	Q5RJ85
	HLA-G	NM_001384280.1		c.475delC	p.Leu159CysfsTer60	frameshift	Exon 5 of 9	NP_001371209.1	Q5RJ85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.460delC	p.Leu154CysfsTer60	frameshift	Exon 3 of 7	ENSP00000353472.6	P17693-1
	HLA-G	ENST00000376828.6	TSL:6	c.475delC	p.Leu159CysfsTer60	frameshift	Exon 4 of 8	ENSP00000366024.2	Q5RJ85
	HLA-G	ENST00000936944.1		c.460delC	p.Leu154CysfsTer60	frameshift	Exon 3 of 7	ENSP00000607003.1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4276 AN: 152178 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.0194

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0167 AC: 4149 AN: 247946 AF XY: 0.0164

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.0144

Gnomad ASJ exome AF: 0.0218

Gnomad EAS exome AF: 0.0189

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0130 AC: 18956 AN: 1461164 Hom.: 246 Cov.: 44 AF XY: 0.0131 AC XY: 9543 AN XY: 726922

African (AFR) AF: 0.0741 AC: 2482 AN: 33480

American (AMR) AF: 0.0146 AC: 651 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0203 AC: 530 AN: 26136

East Asian (EAS) AF: 0.0115 AC: 457 AN: 39700

South Asian (SAS) AF: 0.0149 AC: 1281 AN: 86258

European-Finnish (FIN) AF: 0.00199 AC: 105 AN: 52698

Middle Eastern (MID) AF: 0.0328 AC: 189 AN: 5768

European-Non Finnish (NFE) AF: 0.0110 AC: 12204 AN: 1112008

Other (OTH) AF: 0.0175 AC: 1057 AN: 60392

GnomAD4 genome AF: 0.0281 AC: 4275 AN: 152296 Hom.: 101 Cov.: 32 AF XY: 0.0275 AC XY: 2045 AN XY: 74484

African (AFR) AF: 0.0685 AC: 2845 AN: 41562

American (AMR) AF: 0.0181 AC: 277 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3470

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5182

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4826

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10626

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 830 AN: 68004

Other (OTH) AF: 0.0322 AC: 68 AN: 2114

Alfa AF: 0.00668 Hom.: 8

Bravo AF: 0.0332

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.0161

EpiControl AF: 0.0168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.53
Mutation Taster		=195/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41557518;

hg19: chr6-29796434;

COSMIC: COSV64406193;

COSMIC: COSV64406193;