3-68863380-A-G

Variant names:

• chr3-68863380-A-G
• rs923512
• NM_182522.5:c.130+17350T>C

Variant summary

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

The NM_182522.5(TAFA4):​c.130+17350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,166 control chromosomes in the GnomAD database, including 3,434 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 0.17 (3434 hom., cov: 32)
• Consequence: TAFA4 NM_182522.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA4	NM_182522.5	c.130+17350T>C		intron_variant	Intron 3 of 5	ENST00000295569.12	NP_872328.1
TAFA4	NM_001005527.3	c.130+17350T>C		intron_variant	Intron 3 of 5		NP_001005527.1
TAFA4	XM_011533371.2	c.130+17350T>C		intron_variant	Intron 3 of 5		XP_011531673.1
TAFA4	XM_011533372.2	c.130+17350T>C		intron_variant	Intron 3 of 5		XP_011531674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA4	ENST00000295569.12	c.130+17350T>C		intron_variant	Intron 3 of 5	1	NM_182522.5	ENSP00000295569.7
TAFA4	ENST00000495737.1	c.130+17350T>C		intron_variant	Intron 3 of 3	4		ENSP00000419439.1
TAFA4	ENST00000634242.1	c.130+17350T>C		intron_variant	Intron 6 of 6	5		ENSP00000489092.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25877 AN: 152048 Hom.: 3429 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.170 AC: 25887 AN: 152166 Hom.: 3434 Cov.: 32 AF XY: 0.181 AC XY: 13426 AN XY: 74378

African (AFR) AF: 0.0625 AC: 2598 AN: 41554

American (AMR) AF: 0.294 AC: 4487 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3470

East Asian (EAS) AF: 0.619 AC: 3190 AN: 5152

South Asian (SAS) AF: 0.432 AC: 2083 AN: 4824

European-Finnish (FIN) AF: 0.179 AC: 1893 AN: 10592

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10639 AN: 67976

Other (OTH) AF: 0.172 AC: 364 AN: 2112

Alfa AF: 0.172 Hom.: 1442

Bravo AF: 0.171

Asia WGS AF: 0.485 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	0.78
PhyloP100		-0.61
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: rs923512; hg19: chr3-68912531;