dbSNP rs1043620: HSPA1A:p.Ile74Ile (chr6-31815978-T-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_005345.6(HSPA1A):c.222T>A(p.Ile74Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 13)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HSPA1A
NM_005345.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.936

Publications

18 publications found

Variant links:

Genes affected

HSPA1A (HGNC:5232): (heat shock protein family A (Hsp70) member 1A) This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction 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. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]

HSPA1A links:

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]

HSPA1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=-0.936 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005345.6. 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
	HSPA1A	NM_005345.6	MANE Select	c.222T>A	p.Ile74Ile	synonymous	Exon 1 of 1	NP_005336.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSPA1A	ENST00000375651.7	TSL:6 MANE Select	c.222T>A	p.Ile74Ile	synonymous	Exon 1 of 1	ENSP00000364802.5	P0DMV8-1
HSPA1A	ENST00000608703.2	TSL:2	c.75+147T>A		intron	N/A	ENSP00000477378.1	V9GZ37
HSPA1L	ENST00000879288.1		c.-411A>T		upstream_gene	N/A	ENSP00000549347.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

119028

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1330976

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654418

African (AFR)

AF:

0.00

AC:

AN:

30274

American (AMR)

AF:

0.00

AC:

AN:

34222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23028

East Asian (EAS)

AF:

0.00

AC:

AN:

35266

South Asian (SAS)

AF:

0.00

AC:

AN:

75352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3878

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1030238

Other (OTH)

AF:

0.00

AC:

AN:

55364

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

119120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

55936

African (AFR)

AF:

0.00

AC:

AN:

30236

American (AMR)

AF:

0.00

AC:

AN:

11346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3088

East Asian (EAS)

AF:

0.00

AC:

AN:

4088

South Asian (SAS)

AF:

0.00

AC:

AN:

3060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57590

Other (OTH)

AF:

0.00

AC:

AN:

1478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.6

(source)

DANN

Benign

0.93

PhyloP100

-0.94

PromoterAI

0.066

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over