rs28546865

Variant names:

• chr8-72069083-G-A
• rs28546865
• NM_007332.3:c.384C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-72069083-G-A
• chr8-72069083-G-T

Variant summary

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

The NM_007332.3(TRPA1):​c.384C>T​(p.Asn128Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,846 control chromosomes in the GnomAD database, including 15,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (2452 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12624 hom.)
• Consequence: TRPA1 NM_007332.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.28
• Publications: 11 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 8-72069083-G-A is Benign according to our data. Variant chr8-72069083-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058871.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007332.3. 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
	TRPA1	NM_007332.3	MANE Select	c.384C>T	p.Asn128Asn	synonymous	Exon 3 of 27	NP_015628.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.384C>T	p.Asn128Asn	synonymous	Exon 3 of 27	ENSP00000262209.4
	TRPA1	ENST00000859810.1		c.384C>T	p.Asn128Asn	synonymous	Exon 5 of 29	ENSP00000529869.1
	MSC-AS1	ENST00000518916.5	TSL:3	n.470-7438G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24537 AN: 152028 Hom.: 2445 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.156

GnomAD2 exomes AF: 0.138 AC: 34765 AN: 251478 AF XY: 0.139

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.0693

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.305

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.123 AC: 179123 AN: 1461700 Hom.: 12624 Cov.: 37 AF XY: 0.124 AC XY: 90052 AN XY: 727138

African (AFR) AF: 0.278 AC: 9314 AN: 33476

American (AMR) AF: 0.0706 AC: 3159 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3548 AN: 26136

East Asian (EAS) AF: 0.312 AC: 12369 AN: 39700

South Asian (SAS) AF: 0.181 AC: 15610 AN: 86254

European-Finnish (FIN) AF: 0.112 AC: 6002 AN: 53420

Middle Eastern (MID) AF: 0.129 AC: 742 AN: 5766

European-Non Finnish (NFE) AF: 0.108 AC: 120545 AN: 1111834

Other (OTH) AF: 0.130 AC: 7834 AN: 60390

GnomAD4 genome AF: 0.161 AC: 24558 AN: 152146 Hom.: 2452 Cov.: 32 AF XY: 0.161 AC XY: 11938 AN XY: 74380

African (AFR) AF: 0.276 AC: 11429 AN: 41470

American (AMR) AF: 0.0891 AC: 1363 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1482 AN: 5178

South Asian (SAS) AF: 0.179 AC: 864 AN: 4814

European-Finnish (FIN) AF: 0.109 AC: 1159 AN: 10596

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7333 AN: 67996

Other (OTH) AF: 0.157 AC: 332 AN: 2116

Alfa AF: 0.131 Hom.: 797

Bravo AF: 0.163

Asia WGS AF: 0.192 AC: 668 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.108

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TRPA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		2.3
Mutation Taster		=99/1	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: rs28546865; hg19: chr8-72981318; COSMIC: COSV51569245; COSMIC: COSV51569245;