NM_001374675.1:c.124-66C>A

Variant names:

• chr16-67165456-C-A
• rs115471631
• NM_001374675.1:c.124-66C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001374675.1(HSF4):​c.124-66C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: HSF4 NM_001374675.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882

Genes affected

HSF4 (HGNC:5227): (heat shock transcription factor 4) Heat-shock transcription factors (HSFs) activate heat-shock response genes under conditions of heat or other stresses. HSF4 lacks the carboxyl-terminal hydrophobic repeat which is shared among all vertebrate HSFs and has been suggested to be involved in the negative regulation of DNA binding activity. Two alternatively spliced transcripts encoding distinct isoforms and possessing different transcriptional activity have been described. [provided by RefSeq, Jul 2008]

ENSG00000265690 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSF4	NM_001374675.1	c.124-66C>A		intron_variant	Intron 1 of 12	ENST00000521374.6	NP_001361604.1
HSF4	NM_001040667.3	c.124-66C>A		intron_variant	Intron 3 of 14		NP_001035757.1
HSF4	NM_001374674.1	c.124-66C>A		intron_variant	Intron 1 of 12		NP_001361603.1
HSF4	NM_001538.4	c.124-66C>A		intron_variant	Intron 3 of 14		NP_001529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSF4	ENST00000521374.6	c.124-66C>A		intron_variant	Intron 1 of 12	1	NM_001374675.1	ENSP00000430947.2
ENSG00000265690	ENST00000580114.5	n.*653-66C>A		intron_variant	Intron 3 of 4	5		ENSP00000464271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 19

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.2
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs115471631; hg19: chr16-67199359;