NM_052970.5:c.44-6C>T

Variant names:

• chr20-3740809-C-T
• rs3827077
• NM_052970.5:c.44-6C>T

Variant summary

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

The NM_052970.5(HSPA12B):​c.44-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,611,748 control chromosomes in the GnomAD database, including 34,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4653 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29654 hom.)
• Consequence: HSPA12B NM_052970.5 splice_region, intron
• Scores: Splicing: ADA: 0.0001956
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 14 publications found

Genes affected

HSPA12B (HGNC:16193): (heat shock protein family A (Hsp70) member 12B) The protein encoded by this gene contains an atypical heat shock protein 70 (Hsp70) ATPase domain and is therefore a distant member of the mammalian Hsp70 family. This gene may be involved in susceptibility to atherosclerosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052970.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA12B	NM_052970.5	MANE Select	c.44-6C>T		splice_region intron	N/A	NP_443202.3
	HSPA12B	NM_001197327.2		c.44-6C>T		splice_region intron	N/A	NP_001184256.1
	HSPA12B	NM_001318322.2		c.-117-1475C>T		intron	N/A	NP_001305251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA12B	ENST00000254963.7	TSL:1 MANE Select	c.44-6C>T		splice_region intron	N/A	ENSP00000254963.2
	HSPA12B	ENST00000399701.1	TSL:1	c.-117-1475C>T		intron	N/A	ENSP00000382608.1
	HSPA12B	ENST00000887993.1		c.44-6C>T		splice_region intron	N/A	ENSP00000558052.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35293 AN: 152014 Hom.: 4642 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0913

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.247

GnomAD2 exomes AF: 0.192 AC: 47342 AN: 246560 AF XY: 0.190

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.134

Gnomad FIN exome AF: 0.0925

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.197 AC: 287752 AN: 1459614 Hom.: 29654 Cov.: 32 AF XY: 0.197 AC XY: 142789 AN XY: 726006

African (AFR) AF: 0.351 AC: 11730 AN: 33436

American (AMR) AF: 0.205 AC: 9110 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 6003 AN: 26072

East Asian (EAS) AF: 0.187 AC: 7428 AN: 39648

South Asian (SAS) AF: 0.210 AC: 18039 AN: 86024

European-Finnish (FIN) AF: 0.0981 AC: 5196 AN: 52976

Middle Eastern (MID) AF: 0.263 AC: 1516 AN: 5760

European-Non Finnish (NFE) AF: 0.195 AC: 216464 AN: 1110886

Other (OTH) AF: 0.203 AC: 12266 AN: 60296

GnomAD4 genome AF: 0.232 AC: 35330 AN: 152134 Hom.: 4653 Cov.: 32 AF XY: 0.226 AC XY: 16791 AN XY: 74380

African (AFR) AF: 0.347 AC: 14380 AN: 41472

American (AMR) AF: 0.236 AC: 3612 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 838 AN: 3472

East Asian (EAS) AF: 0.150 AC: 775 AN: 5154

South Asian (SAS) AF: 0.195 AC: 942 AN: 4828

European-Finnish (FIN) AF: 0.0913 AC: 969 AN: 10612

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12860 AN: 68008

Other (OTH) AF: 0.251 AC: 531 AN: 2112

Alfa AF: 0.214 Hom.: 3508

Bravo AF: 0.249

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00020
dbscSNV1_RF	Benign	0.016
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: rs3827077; hg19: chr20-3721456; COSMIC: COSV54767159;