chr8-72029895-A-G

Variant names:

• chr8-72029895-A-G
• rs186828882
• NM_007332.3:c.2937+6T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_007332.3(TRPA1):​c.2937+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,613,732 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (36 hom.)
• Consequence: TRPA1 NM_007332.3 splice_region, intron
• Scores: Splicing: ADA: 0.1393
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.37
• Publications: 1 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=-0.45).
• BP6: Variant 8-72029895-A-G is Benign according to our data. Variant chr8-72029895-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 788822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 535 AD,Unknown gene.

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.2937+6T>C		splice_region intron	N/A	NP_015628.2	O75762
	MSC-AS1	NR_033651.1		n.434-22644A>G		intron	N/A
	MSC-AS1	NR_033652.1		n.1029-22644A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.2937+6T>C		splice_region intron	N/A	ENSP00000262209.4	O75762
	MSC-AS1	ENST00000457356.9	TSL:1	n.511-22644A>G		intron	N/A
	TRPA1	ENST00000859810.1		c.2937+6T>C		splice_region intron	N/A	ENSP00000529869.1

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 152198 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00460

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00436 AC: 1095 AN: 251014 AF XY: 0.00456

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00854

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.00490

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00454 AC: 6639 AN: 1461416 Hom.: 36 Cov.: 30 AF XY: 0.00455 AC XY: 3311 AN XY: 727030

African (AFR) AF: 0.000568 AC: 19 AN: 33466

American (AMR) AF: 0.00163 AC: 73 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00823 AC: 215 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00218 AC: 188 AN: 86244

European-Finnish (FIN) AF: 0.0134 AC: 718 AN: 53410

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5760

European-Non Finnish (NFE) AF: 0.00459 AC: 5106 AN: 1111636

Other (OTH) AF: 0.00518 AC: 313 AN: 60374

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152316 Hom.: 2 Cov.: 32 AF XY: 0.00365 AC XY: 272 AN XY: 74484

African (AFR) AF: 0.000505 AC: 21 AN: 41578

American (AMR) AF: 0.00150 AC: 23 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.0130 AC: 138 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00460 AC: 313 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00414 Hom.: 1

Bravo AF: 0.00264

EpiCase AF: 0.00360

EpiControl AF: 0.00415

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.1
DANN	Benign	0.93
PhyloP100		2.4
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.14
dbscSNV1_RF	Benign	0.28
Splicevardb		2.0
SpliceAI score (max)		0.19		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: rs186828882; hg19: chr8-72942130;