chr16-166743-C-A

Position:

• chr16-166743-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000356815.4(HBM):​c.*35C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,610,788 control chromosomes in the GnomAD database, including 179 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 0.0038 (26 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (153 hom.)
• Consequence: HBM ENST00000356815.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.930

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HBM	NM_001003938.4	c.*35C>A		3_prime_UTR_variant	3/3	ENST00000356815.4	NP_001003938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HBM	ENST00000356815.4	c.*35C>A		3_prime_UTR_variant	3/3	1	NM_001003938.4	ENSP00000349270	P1
HBM	ENST00000472539.5	n.574C>A		non_coding_transcript_exon_variant	3/3	5
HBM	ENST00000496585.1	n.574C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.00384 AC: 584 AN: 152178 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.00255

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00919 AC: 2238 AN: 243478 Hom.: 85 AF XY: 0.00803 AC XY: 1058 AN XY: 131802

Gnomad AFR exome AF: 0.000128

Gnomad AMR exome AF: 0.0164

Gnomad ASJ exome AF: 0.00354

Gnomad EAS exome AF: 0.0792

Gnomad SAS exome AF: 0.00259

Gnomad FIN exome AF: 0.00301

Gnomad NFE exome AF: 0.000457

Gnomad OTH exome AF: 0.00534

GnomAD4 exome AF: 0.00306 AC: 4469 AN: 1458492 Hom.: 153 Cov.: 34 AF XY: 0.00296 AC XY: 2150 AN XY: 725322

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.0144

Gnomad4 ASJ exome AF: 0.00322

Gnomad4 EAS exome AF: 0.0713

Gnomad4 SAS exome AF: 0.00333

Gnomad4 FIN exome AF: 0.00314

Gnomad4 NFE exome AF: 0.000197

Gnomad4 OTH exome AF: 0.00422

GnomAD4 genome AF: 0.00383 AC: 584 AN: 152296 Hom.: 26 Cov.: 33 AF XY: 0.00410 AC XY: 305 AN XY: 74476

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.0786

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.00255

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00185 Hom.: 1

Bravo AF: 0.00484

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.0
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs75368786; hg19: chr16-216742; COSMIC: COSV61575242; COSMIC: COSV61575242;