chr21-43658154-C-T

Variant names:

• chr21-43658154-C-T
• rs2838343
• NM_007031.2:c.-58G>A

Variant summary

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

The NM_007031.2(HSF2BP):​c.-58G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,469,810 control chromosomes in the GnomAD database, including 247,111 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 0.58 (26390 hom., cov: 35)
  • Exomes 𝑓: 0.58 (220721 hom.)
• Consequence: HSF2BP NM_007031.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 14 publications found

Genes affected

HSF2BP (HGNC:5226): (heat shock transcription factor 2 binding protein) HSF2 binding protein (HSF2BP) associates with HSF2. The interaction occurs between the trimerization domain of HSF2 and the amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper motifs. HSF2BP may therefore be involved in modulating HSF2 activation. [provided by RefSeq, Jul 2008]

HSF2BP Gene-Disease associations (from GenCC):

• premature ovarian failure 19

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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 (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSF2BP	NM_007031.2	c.-58G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	ENST00000291560.7	NP_008962.1
HSF2BP	NM_007031.2	c.-58G>A		5_prime_UTR_variant	Exon 2 of 9	ENST00000291560.7	NP_008962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSF2BP	ENST00000291560.7	c.-58G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	1	NM_007031.2	ENSP00000291560.2
HSF2BP	ENST00000291560.7	c.-58G>A		5_prime_UTR_variant	Exon 2 of 9	1	NM_007031.2	ENSP00000291560.2
HSF2BP	ENST00000443485.1	c.-58G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 7	5		ENSP00000409585.1
HSF2BP	ENST00000443485.1	c.-58G>A		5_prime_UTR_variant	Exon 2 of 7	5		ENSP00000409585.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88817 AN: 152068 Hom.: 26359 Cov.: 35

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.576 AC: 758625 AN: 1317624 Hom.: 220721 Cov.: 30 AF XY: 0.577 AC XY: 371958 AN XY: 644162

African (AFR) AF: 0.520 AC: 14657 AN: 28196

American (AMR) AF: 0.728 AC: 18913 AN: 25976

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 13285 AN: 21666

East Asian (EAS) AF: 0.780 AC: 26213 AN: 33620

South Asian (SAS) AF: 0.652 AC: 46129 AN: 70766

European-Finnish (FIN) AF: 0.662 AC: 21501 AN: 32500

Middle Eastern (MID) AF: 0.606 AC: 3283 AN: 5418

European-Non Finnish (NFE) AF: 0.558 AC: 582507 AN: 1044618

Other (OTH) AF: 0.586 AC: 32137 AN: 54864

GnomAD4 genome AF: 0.584 AC: 88904 AN: 152186 Hom.: 26390 Cov.: 35 AF XY: 0.595 AC XY: 44298 AN XY: 74422

African (AFR) AF: 0.522 AC: 21692 AN: 41526

American (AMR) AF: 0.676 AC: 10343 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2115 AN: 3472

East Asian (EAS) AF: 0.784 AC: 4051 AN: 5166

South Asian (SAS) AF: 0.668 AC: 3221 AN: 4822

European-Finnish (FIN) AF: 0.664 AC: 7037 AN: 10598

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38525 AN: 67986

Other (OTH) AF: 0.583 AC: 1230 AN: 2110

Alfa AF: 0.559 Hom.: 10312

Bravo AF: 0.579

Asia WGS AF: 0.731 AC: 2542 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	14
DANN	Benign	0.95
PhyloP100		0.13
Mutation Taster		=300/0	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: rs2838343; hg19: chr21-45078035; COSMIC: COSV52360104; COSMIC: COSV52360104;