rs12658558

Variant names:

• chr5-156960640-C-T
• rs12658558
• NM_138379.3:c.58+2501G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138379.3(TIMD4):​c.58+2501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 152,192 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.028 (188 hom., cov: 31)
• Consequence: TIMD4 NM_138379.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 1 publications found

Genes affected

TIMD4 (HGNC:25132): (T cell immunoglobulin and mucin domain containing 4) Predicted to enable phosphatidylserine binding activity. Predicted to act upstream of or within apoptotic cell clearance. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138379.3. 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
	TIMD4	NM_138379.3	MANE Select	c.58+2501G>A		intron	N/A	NP_612388.2	Q96H15-1
	TIMD4	NM_001146726.2		c.58+2501G>A		intron	N/A	NP_001140198.1	Q96H15-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMD4	ENST00000274532.7	TSL:1 MANE Select	c.58+2501G>A		intron	N/A	ENSP00000274532.2	Q96H15-1
	TIMD4	ENST00000407087.4	TSL:2	c.58+2501G>A		intron	N/A	ENSP00000385973.3	Q96H15-2

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4328 AN: 152074 Hom.: 185 Cov.: 31

Gnomad AFR AF: 0.00592

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0285 AC: 4333 AN: 152192 Hom.: 188 Cov.: 31 AF XY: 0.0315 AC XY: 2347 AN XY: 74396

African (AFR) AF: 0.00590 AC: 245 AN: 41538

American (AMR) AF: 0.114 AC: 1738 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.101 AC: 521 AN: 5170

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4814

European-Finnish (FIN) AF: 0.0325 AC: 344 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0197 AC: 1342 AN: 67994

Other (OTH) AF: 0.0284 AC: 60 AN: 2110

Alfa AF: 0.0215 Hom.: 12

Bravo AF: 0.0344

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-2.3
Mutation Taster		=100/0	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: rs12658558; hg19: chr5-156387651; COSMIC: COSV50857858;