rs373922488

Variant names:

• chr2-70216386-C-A
• rs373922488
• NM_022173.4:c.679+18G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-70216386-C-A
• chr2-70216386-C-G
• chr2-70216386-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_022173.4(TIA1):​c.679+18G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,600,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: TIA1 NM_022173.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0920
• 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-70216386-C-A is Benign according to our data. Variant chr2-70216386-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 123 AD,Unknown,SD 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.679+18G>T		intron	N/A	NP_071505.2	P31483-1
	TIA1	NM_001351508.2		c.679+18G>T		intron	N/A	NP_001338437.1	F8W8I6
	TIA1	NM_001351509.2		c.652+18G>T		intron	N/A	NP_001338438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIA1	ENST00000433529.7	TSL:2 MANE Select	c.679+18G>T		intron	N/A	ENSP00000401371.2	P31483-1
	TIA1	ENST00000415783.6	TSL:1	c.646+18G>T		intron	N/A	ENSP00000404023.2	P31483-2
	TIA1	ENST00000881363.1		c.775+18G>T		intron	N/A	ENSP00000551422.1

Frequencies

GnomAD3 genomes AF: 0.000808 AC: 123 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000549 AC: 133 AN: 242322 AF XY: 0.000527

Gnomad AFR exome AF: 0.000374

Gnomad AMR exome AF: 0.000189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.000509

GnomAD4 exome AF: 0.00122 AC: 1764 AN: 1448790 Hom.: 2 Cov.: 30 AF XY: 0.00113 AC XY: 812 AN XY: 720552

African (AFR) AF: 0.000244 AC: 8 AN: 32810

American (AMR) AF: 0.000192 AC: 8 AN: 41766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25716

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00 AC: 0 AN: 83400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00155 AC: 1715 AN: 1106664

Other (OTH) AF: 0.000551 AC: 33 AN: 59882

GnomAD4 genome AF: 0.000808 AC: 123 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.000726 AC XY: 54 AN XY: 74354

African (AFR) AF: 0.000434 AC: 18 AN: 41454

American (AMR) AF: 0.000262 AC: 4 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00148 AC: 101 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.000805

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.72
DANN	Benign	0.39
PhyloP100		-0.092
Mutation Taster		=100/0	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: rs373922488; hg19: chr2-70443518;