chr3-68885283-T-G

Position:

• chr3-68885283-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_182522.5(TAFA4):​c.-95A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,201,552 control chromosomes in the GnomAD database, including 22,778 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 0.16 (2830 hom., cov: 32)
  • Exomes 𝑓: 0.17 (19948 hom.)
• Consequence: TAFA4 NM_182522.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523

Genes affected

TAFA4 (HGNC:21591): (TAFA chemokine like family member 4) This gene is a member of the TAFA family which is composed of five highly homologous genes that encode small secreted proteins. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines, that act as regulators of immune and nervous cells. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAFA4	NM_182522.5	c.-95A>C		5_prime_UTR_variant	2/6	ENST00000295569.12	NP_872328.1
TAFA4	NM_001005527.3	c.-95A>C		5_prime_UTR_variant	2/6		NP_001005527.1
TAFA4	XM_011533371.2	c.-95A>C		5_prime_UTR_variant	2/6		XP_011531673.1
TAFA4	XM_011533372.2	c.-95A>C		5_prime_UTR_variant	2/6		XP_011531674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFA4	ENST00000295569.12	c.-95A>C		5_prime_UTR_variant	2/6	1	NM_182522.5	ENSP00000295569.7
TAFA4	ENST00000495737.1	c.-95A>C		5_prime_UTR_variant	2/4	4		ENSP00000419439.1
TAFA4	ENST00000634242.1	c.-95A>C		5_prime_UTR_variant	5/7	5		ENSP00000489092.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24686 AN: 151080 Hom.: 2824 Cov.: 32

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.0909

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.170 AC: 178591 AN: 1050360 Hom.: 19948 Cov.: 13 AF XY: 0.174 AC XY: 92614 AN XY: 531340

Gnomad4 AFR exome AF: 0.0652

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.0858

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.163 AC: 24707 AN: 151192 Hom.: 2830 Cov.: 32 AF XY: 0.173 AC XY: 12749 AN XY: 73824

Gnomad4 AFR AF: 0.0777

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.0909

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.162

Alfa AF: 0.158 Hom.: 3137

Bravo AF: 0.165

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.9
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs4855535; hg19: chr3-68934434;