rs1741820

Positions:

• chr6-122400365-A-G

Variant summary

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

The NM_004506.4(HSF2):​c.93+535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,052 control chromosomes in the GnomAD database, including 23,679 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 0.56 (23679 hom., cov: 32)
• Consequence: HSF2 NM_004506.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164

Genes affected

HSF2 (HGNC:5225): (heat shock transcription factor 2) The protein encoded by this gene belongs to the HSF family of transcription factors that bind specifically to the heat-shock promoter element and activate transcription. Heat shock transcription factors activate heat-shock response genes under conditions of heat or other stresses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSF2	NM_004506.4	c.93+535A>G		intron_variant		ENST00000368455.9
HSF2	NM_001135564.1	c.93+535A>G		intron_variant
HSF2	NM_001243094.2	c.93+535A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSF2	ENST00000368455.9	c.93+535A>G		intron_variant		1	NM_004506.4	P1
HSF2	ENST00000452194.5	c.93+535A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84459 AN: 151934 Hom.: 23678 Cov.: 32

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.548

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.556 AC: 84488 AN: 152052 Hom.: 23679 Cov.: 32 AF XY: 0.559 AC XY: 41528 AN XY: 74308

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.678

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.548

Alfa AF: 0.557 Hom.: 30835

Bravo AF: 0.556

Asia WGS AF: 0.573 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.62

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: rs1741820; hg19: chr6-122721510;