rs2075799

Variant names:

• chr6-31810752-C-T
• rs2075799
• NM_005527.4:c.1221G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31810752-C-T
• chr6-31810752-C-A
• chr6-31810752-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_005527.4(HSPA1L):​c.1221G>A​(p.Thr407Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 1,613,840 control chromosomes in the GnomAD database, including 7,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1599 hom., cov: 32)
  • Exomes 𝑓: 0.080 (6194 hom.)
• Consequence: HSPA1L NM_005527.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -9.35
• Publications: 64 publications found

Genes affected

HSPA1L (HGNC:5234): (heat shock protein family A (Hsp70) member 1 like) This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-31810752-C-T is Benign according to our data. Variant chr6-31810752-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059212.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-9.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005527.4. 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
	HSPA1L	NM_005527.4	MANE Select	c.1221G>A	p.Thr407Thr	synonymous	Exon 2 of 2	NP_005518.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1L	ENST00000375654.5	TSL:1 MANE Select	c.1221G>A	p.Thr407Thr	synonymous	Exon 2 of 2	ENSP00000364805.4	P34931
	HSPA1L	ENST00000879288.1		c.1221G>A	p.Thr407Thr	synonymous	Exon 2 of 2	ENSP00000549347.1
	HSPA1L	ENST00000879289.1		c.1221G>A	p.Thr407Thr	synonymous	Exon 2 of 2	ENSP00000549348.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19142 AN: 151848 Hom.: 1592 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.103 AC: 25959 AN: 251410 AF XY: 0.0982

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.0408

Gnomad NFE exome AF: 0.0744

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.0800 AC: 116982 AN: 1461874 Hom.: 6194 Cov.: 37 AF XY: 0.0798 AC XY: 58070 AN XY: 727240

African (AFR) AF: 0.218 AC: 7306 AN: 33480

American (AMR) AF: 0.130 AC: 5833 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5902 AN: 26136

East Asian (EAS) AF: 0.155 AC: 6143 AN: 39700

South Asian (SAS) AF: 0.0821 AC: 7079 AN: 86258

European-Finnish (FIN) AF: 0.0408 AC: 2180 AN: 53408

Middle Eastern (MID) AF: 0.142 AC: 821 AN: 5768

European-Non Finnish (NFE) AF: 0.0680 AC: 75636 AN: 1112004

Other (OTH) AF: 0.101 AC: 6082 AN: 60396

GnomAD4 genome AF: 0.126 AC: 19164 AN: 151966 Hom.: 1599 Cov.: 32 AF XY: 0.125 AC XY: 9286 AN XY: 74254

African (AFR) AF: 0.214 AC: 8876 AN: 41380

American (AMR) AF: 0.141 AC: 2155 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 773 AN: 3472

East Asian (EAS) AF: 0.176 AC: 910 AN: 5158

South Asian (SAS) AF: 0.0956 AC: 461 AN: 4822

European-Finnish (FIN) AF: 0.0422 AC: 447 AN: 10594

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0757 AC: 5144 AN: 67958

Other (OTH) AF: 0.156 AC: 330 AN: 2114

Alfa AF: 0.100 Hom.: 4068

Bravo AF: 0.141

Asia WGS AF: 0.119 AC: 414 AN: 3478

EpiCase AF: 0.0883

EpiControl AF: 0.0908

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HSPA1L-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.019
DANN	Benign	0.48
PhyloP100		-9.4
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: rs2075799; hg19: chr6-31778529; COSMIC: COSV65149011; COSMIC: COSV65149011;