8-72063566-T-G

Variant names:

• chr8-72063566-T-G
• rs7819749
• NM_007332.3:c.558A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007332.3(TRPA1):​c.558A>C​(p.Lys186Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,608,096 control chromosomes in the GnomAD database, including 342,578 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (41483 hom., cov: 31)
  • Exomes 𝑓: 0.64 (301095 hom.)
• Consequence: TRPA1 NM_007332.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.535
• Publications: 40 publications found

Genes affected

TRPA1 (HGNC:497): (transient receptor potential cation channel subfamily A member 1) The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq, Jul 2008]

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.347031E-7).
• BP6: Variant 8-72063566-T-G is Benign according to our data. Variant chr8-72063566-T-G is described in ClinVar as Benign. ClinVar VariationId is 1342284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPA1	NM_007332.3	c.558A>C	p.Lys186Asn	missense_variant	Exon 5 of 27	ENST00000262209.5	NP_015628.2
TRPA1	XM_011517624.3	c.633A>C	p.Lys211Asn	missense_variant	Exon 6 of 28		XP_011515926.1
TRPA1	XM_011517625.3	c.558A>C	p.Lys186Asn	missense_variant	Exon 7 of 29		XP_011515927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5	c.558A>C	p.Lys186Asn	missense_variant	Exon 5 of 27	1	NM_007332.3	ENSP00000262209.4

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109810 AN: 151974 Hom.: 41431 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.705 AC: 176918 AN: 251112 AF XY: 0.693

Gnomad AFR exome AF: 0.919

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.990

Gnomad FIN exome AF: 0.630

Gnomad NFE exome AF: 0.604

Gnomad OTH exome AF: 0.651

GnomAD4 exome AF: 0.636 AC: 926101 AN: 1456004 Hom.: 301095 Cov.: 31 AF XY: 0.637 AC XY: 461292 AN XY: 724616

African (AFR) AF: 0.923 AC: 30784 AN: 33348

American (AMR) AF: 0.806 AC: 36007 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 17711 AN: 26060

East Asian (EAS) AF: 0.982 AC: 38903 AN: 39604

South Asian (SAS) AF: 0.737 AC: 63520 AN: 86158

European-Finnish (FIN) AF: 0.635 AC: 33791 AN: 53238

Middle Eastern (MID) AF: 0.654 AC: 3759 AN: 5748

European-Non Finnish (NFE) AF: 0.598 AC: 661779 AN: 1106994

Other (OTH) AF: 0.662 AC: 39847 AN: 60182

GnomAD4 genome AF: 0.723 AC: 109922 AN: 152092 Hom.: 41483 Cov.: 31 AF XY: 0.725 AC XY: 53908 AN XY: 74336

African (AFR) AF: 0.918 AC: 38097 AN: 41516

American (AMR) AF: 0.744 AC: 11359 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2348 AN: 3472

East Asian (EAS) AF: 0.978 AC: 5075 AN: 5190

South Asian (SAS) AF: 0.751 AC: 3614 AN: 4814

European-Finnish (FIN) AF: 0.615 AC: 6496 AN: 10560

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.599 AC: 40712 AN: 67958

Other (OTH) AF: 0.709 AC: 1495 AN: 2110

Alfa AF: 0.650 Hom.: 103756

Bravo AF: 0.742

TwinsUK AF: 0.598 AC: 2217

ESP6500AA AF: 0.917 AC: 4042

ESP6500EA AF: 0.602 AC: 5176

ExAC AF: 0.703 AC: 85357

Asia WGS AF: 0.838 AC: 2913 AN: 3476

EpiCase AF: 0.590

EpiControl AF: 0.589

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Familial episodic pain syndrome with predominantly upper body involvement Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.9
DANN	Benign	0.78
DEOGEN2	Benign	0.0	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
LIST_S2	Benign	0.042	T;T
MetaRNN	Benign	7.3e-7	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	.;N
PhyloP100		-0.54
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.11	N;N
Sift	Benign	0.47	T;T
Sift4G	Benign	0.79	T;T
Vest4		0.0
ClinPred		0.021	T
GERP RS		-11
Varity_R		0.043
gMVP		0.17
Mutation Taster		=97/3	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: rs7819749; hg19: chr8-72975801; COSMIC: COSV107262311; COSMIC: COSV107262311;