chr6-122400365-A-G

Variant names:

• chr6-122400365-A-G
• rs1741820
• NM_004506.4:c.93+535A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HSF2	NM_004506.4	c.93+535A>G		intron_variant	Intron 1 of 12	ENST00000368455.9	NP_004497.1
HSF2	NM_001135564.1	c.93+535A>G		intron_variant	Intron 1 of 11		NP_001129036.1
HSF2	NM_001243094.2	c.93+535A>G		intron_variant	Intron 1 of 6		NP_001230023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSF2	ENST00000368455.9	c.93+535A>G		intron_variant	Intron 1 of 12	1	NM_004506.4	ENSP00000357440.4
HSF2	ENST00000452194.5	c.93+535A>G		intron_variant	Intron 1 of 11	1		ENSP00000400380.1

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

African (AFR) AF: 0.550 AC: 22795 AN: 41464

American (AMR) AF: 0.620 AC: 9478 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2369 AN: 5148

South Asian (SAS) AF: 0.678 AC: 3265 AN: 4818

European-Finnish (FIN) AF: 0.542 AC: 5737 AN: 10584

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36993 AN: 67964

Other (OTH) AF: 0.548 AC: 1156 AN: 2110

Alfa AF: 0.556 Hom.: 36622

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
PhyloP100		-0.16
Mutation Taster		=100/0	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: rs1741820; hg19: chr6-122721510;