5-156963286-T-C

Variant names:

• chr5-156963286-T-C
• rs6882076
• NM_138379.3:c.-88A>G

Variant summary

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

The NM_138379.3(TIMD4):​c.-88A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,400,670 control chromosomes in the GnomAD database, including 283,865 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 0.57 (26155 hom., cov: 31)
  • Exomes 𝑓: 0.64 (257710 hom.)
• Consequence: TIMD4 NM_138379.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 107 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 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.-88A>G		upstream_gene	N/A	NP_612388.2	Q96H15-1
	TIMD4	NM_001146726.2		c.-88A>G		upstream_gene	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.-88A>G		upstream_gene	N/A	ENSP00000274532.2	Q96H15-1
	TIMD4	ENST00000407087.4	TSL:2	c.-88A>G		upstream_gene	N/A	ENSP00000385973.3	Q96H15-2

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86800 AN: 151852 Hom.: 26139 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.640 AC: 798631 AN: 1248700 Hom.: 257710 Cov.: 16 AF XY: 0.640 AC XY: 404648 AN XY: 632002

African (AFR) AF: 0.355 AC: 10201 AN: 28706

American (AMR) AF: 0.790 AC: 34394 AN: 43558

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 15067 AN: 24462

East Asian (EAS) AF: 0.784 AC: 30181 AN: 38508

South Asian (SAS) AF: 0.662 AC: 53844 AN: 81314

European-Finnish (FIN) AF: 0.663 AC: 35041 AN: 52824

Middle Eastern (MID) AF: 0.539 AC: 2881 AN: 5344

European-Non Finnish (NFE) AF: 0.635 AC: 584357 AN: 920930

Other (OTH) AF: 0.616 AC: 32665 AN: 53054

GnomAD4 genome AF: 0.571 AC: 86844 AN: 151970 Hom.: 26155 Cov.: 31 AF XY: 0.579 AC XY: 43022 AN XY: 74272

African (AFR) AF: 0.366 AC: 15171 AN: 41424

American (AMR) AF: 0.685 AC: 10470 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2123 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3849 AN: 5168

South Asian (SAS) AF: 0.677 AC: 3251 AN: 4804

European-Finnish (FIN) AF: 0.684 AC: 7224 AN: 10558

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.627 AC: 42634 AN: 67960

Other (OTH) AF: 0.585 AC: 1234 AN: 2108

Alfa AF: 0.615 Hom.: 122513

Bravo AF: 0.564

Asia WGS AF: 0.690 AC: 2402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.57
PhyloP100		2.2
PromoterAI		-0.097	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6882076; hg19: chr5-156390297; COSMIC: COSV50854534;