chr16-165856-G-C

Variant names:

• chr16-165856-G-C
• rs2858935
• ENST00000472539.5:n.206-412G>C

Variant summary

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

The ENST00000472539.5(HBM):​n.206-412G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 633,098 control chromosomes in the GnomAD database, including 29,798 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 0.31 (7281 hom., cov: 33)
  • Exomes 𝑓: 0.30 (22517 hom.)
• Consequence: HBM ENST00000472539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 8 publications found

Genes affected

HBM (HGNC:4826): (hemoglobin subunit mu) The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes seven loci: 5'- zeta - pseudozeta - mu - pseudoalpha-1 - alpha-2 - alpha-1 - theta - 3'. This gene has an ORF encoding a 141 aa polypeptide which is similar to the delta globins found in reptiles and birds. This locus was originally described as a pseudogene; however, it is currently thought to be a protein-coding gene. [provided by RefSeq, Jul 2008]

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 (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HBM	NM_001003938.4	c.-142G>C		upstream_gene_variant		ENST00000356815.4	NP_001003938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HBM	ENST00000472539.5	n.206-412G>C		intron_variant	Intron 1 of 2	5
HBM	ENST00000496585.1	n.206-412G>C		intron_variant	Intron 1 of 2	2
HBM	ENST00000356815.4	c.-142G>C		upstream_gene_variant		1	NM_001003938.4	ENSP00000349270.3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46768 AN: 152092 Hom.: 7265 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.302 AC: 145042 AN: 480892 Hom.: 22517 AF XY: 0.305 AC XY: 76922 AN XY: 252006

African (AFR) AF: 0.357 AC: 4477 AN: 12556

American (AMR) AF: 0.299 AC: 6431 AN: 21514

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 4540 AN: 14372

East Asian (EAS) AF: 0.362 AC: 10967 AN: 30288

South Asian (SAS) AF: 0.372 AC: 17660 AN: 47444

European-Finnish (FIN) AF: 0.243 AC: 7213 AN: 29680

Middle Eastern (MID) AF: 0.321 AC: 670 AN: 2084

European-Non Finnish (NFE) AF: 0.287 AC: 84905 AN: 295820

Other (OTH) AF: 0.301 AC: 8179 AN: 27134

GnomAD4 genome AF: 0.308 AC: 46825 AN: 152206 Hom.: 7281 Cov.: 33 AF XY: 0.306 AC XY: 22765 AN XY: 74414

African (AFR) AF: 0.355 AC: 14741 AN: 41528

American (AMR) AF: 0.299 AC: 4582 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1603 AN: 5160

South Asian (SAS) AF: 0.371 AC: 1789 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2575 AN: 10616

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19427 AN: 67988

Other (OTH) AF: 0.314 AC: 664 AN: 2114

Alfa AF: 0.176 Hom.: 353

Bravo AF: 0.312

Asia WGS AF: 0.399 AC: 1387 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	3.8
DANN	Benign	0.22
PhyloP100		-0.72
PromoterAI		0.0049	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2858935; hg19: chr16-215855; COSMIC: COSV61575266;