21-14383500-C-T

Variant names:

• chr21-14383500-C-T
• rs2242661
• ENST00000743737.1:n.775C>T

Variant summary

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

The ENST00000743737.1(ENSG00000296939):​n.775C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 230,488 control chromosomes in the GnomAD database, including 28,136 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 0.47 (17323 hom., cov: 33)
  • Exomes 𝑓: 0.52 (10813 hom.)
• Consequence: ENSG00000296939 ENST00000743737.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 5 publications found

Genes affected

ENSG00000296939 (HGNC:):

HSPA13 (HGNC:11375): (heat shock protein family A (Hsp70) member 13) The protein encoded by this gene is a member of the heat shock protein 70 family and is found associated with microsomes. Members of this protein family play a role in the processing of cytosolic and secretory proteins, as well as in the removal of denatured or incorrectly-folded proteins. The encoded protein contains an ATPase domain and has been shown to associate with a ubiquitin-like protein. [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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000743737.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000296939	ENST00000743737.1		n.775C>T		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000296939	ENST00000743739.1		n.81C>T		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000296939	ENST00000743740.1		n.7C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71146 AN: 151954 Hom.: 17324 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.520 AC: 40757 AN: 78416 Hom.: 10813 Cov.: 0 AF XY: 0.522 AC XY: 21478 AN XY: 41162

African (AFR) AF: 0.312 AC: 781 AN: 2506

American (AMR) AF: 0.408 AC: 886 AN: 2170

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1471 AN: 2702

East Asian (EAS) AF: 0.446 AC: 1758 AN: 3942

South Asian (SAS) AF: 0.519 AC: 4548 AN: 8770

European-Finnish (FIN) AF: 0.544 AC: 2354 AN: 4324

Middle Eastern (MID) AF: 0.563 AC: 205 AN: 364

European-Non Finnish (NFE) AF: 0.539 AC: 26203 AN: 48618

Other (OTH) AF: 0.508 AC: 2551 AN: 5020

GnomAD4 genome AF: 0.468 AC: 71154 AN: 152072 Hom.: 17323 Cov.: 33 AF XY: 0.466 AC XY: 34663 AN XY: 74334

African (AFR) AF: 0.339 AC: 14068 AN: 41488

American (AMR) AF: 0.428 AC: 6547 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1923 AN: 3464

East Asian (EAS) AF: 0.485 AC: 2509 AN: 5176

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4822

European-Finnish (FIN) AF: 0.518 AC: 5469 AN: 10558

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36784 AN: 67958

Other (OTH) AF: 0.480 AC: 1013 AN: 2112

Alfa AF: 0.458 Hom.: 3303

Bravo AF: 0.454

Asia WGS AF: 0.472 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.18
DANN	Benign	0.89
PhyloP100		-2.4
PromoterAI		0.10	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2242661; hg19: chr21-15755821;