rs116828570

Variant names:

• chr2-70214436-G-C
• rs116828570
• NM_022173.4:c.947C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-70214436-G-C
• chr2-70214436-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_022173.4(TIA1):​c.947C>G​(p.Ala316Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00112 in 1,613,906 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (7 hom.)
• Consequence: TIA1 NM_022173.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.53
• Publications: 1 publications found

Genes affected

TIA1 (HGNC:11802): (TIA1 cytotoxic granule associated RNA binding protein) The product encoded by this gene is a member of a RNA-binding protein family and possesses nucleolytic activity against cytotoxic lymphocyte (CTL) target cells. It has been suggested that this protein may be involved in the induction of apoptosis as it preferentially recognizes poly(A) homopolymers and induces DNA fragmentation in CTL targets. The major granule-associated species is a 15-kDa protein that is thought to be derived from the carboxyl terminus of the 40-kDa product by proteolytic processing. Alternative splicing resulting in different isoforms has been found for this gene. [provided by RefSeq, May 2017]

C2orf42 (HGNC:26056): (chromosome 2 open reading frame 42) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.004209727).
• BP6: Variant 2-70214436-G-C is Benign according to our data. Variant chr2-70214436-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 458843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00615 (936/152212) while in subpopulation AFR AF = 0.0215 (892/41538). AF 95% confidence interval is 0.0203. There are 5 homozygotes in GnomAd4. There are 432 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 936 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022173.4. 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
	TIA1	NM_022173.4	MANE Select	c.947C>G	p.Ala316Gly	missense	Exon 12 of 13	NP_071505.2	P31483-1
	TIA1	NM_001351508.2		c.944C>G	p.Ala315Gly	missense	Exon 12 of 13	NP_001338437.1	F8W8I6
	TIA1	NM_001351509.2		c.920C>G	p.Ala307Gly	missense	Exon 11 of 12	NP_001338438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIA1	ENST00000433529.7	TSL:2 MANE Select	c.947C>G	p.Ala316Gly	missense	Exon 12 of 13	ENSP00000401371.2	P31483-1
	TIA1	ENST00000415783.6	TSL:1	c.914C>G	p.Ala305Gly	missense	Exon 11 of 12	ENSP00000404023.2	P31483-2
	TIA1	ENST00000881363.1		c.1043C>G	p.Ala348Gly	missense	Exon 13 of 14	ENSP00000551422.1

Frequencies

GnomAD3 genomes AF: 0.00613 AC: 932 AN: 152094 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

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: 0.0000588

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00162 AC: 407 AN: 251304 AF XY: 0.00110

Gnomad AFR exome AF: 0.0220

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000595 AC: 869 AN: 1461694 Hom.: 7 Cov.: 31 AF XY: 0.000499 AC XY: 363 AN XY: 727162

African (AFR) AF: 0.0212 AC: 711 AN: 33462

American (AMR) AF: 0.00134 AC: 60 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5752

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111938

Other (OTH) AF: 0.00131 AC: 79 AN: 60382

GnomAD4 genome AF: 0.00615 AC: 936 AN: 152212 Hom.: 5 Cov.: 32 AF XY: 0.00581 AC XY: 432 AN XY: 74406

African (AFR) AF: 0.0215 AC: 892 AN: 41538

American (AMR) AF: 0.00203 AC: 31 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67996

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.000445 Hom.: 0

Bravo AF: 0.00697

ESP6500AA AF: 0.0225 AC: 99

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00197 AC: 239

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Welander distal myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.053
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		6.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.051
Sift	Benign	0.52	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.17
MVP		0.24
MPC		0.57
ClinPred		0.013	T
GERP RS		5.2
Varity_R		0.076
gMVP		0.27
Mutation Taster		=90/10	polymorphism

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: rs116828570; hg19: chr2-70441568; COSMIC: COSV99031397; COSMIC: COSV99031397;