rs11615916

Positions:

• chr12-62217079-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000549379.5(TAFA2):​c.-212+41684T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,234 control chromosomes in the GnomAD database, including 1,000 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 0.11 (1000 hom., cov: 32)
• Consequence: TAFA2 ENST00000549379.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

Genes affected

TAFA2 (HGNC:21589): (TAFA chemokine like family member 2) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAFA2	XM_024448962.2	c.146+41684T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAFA2	ENST00000549379.5	c.-212+41684T>C		intron_variant, NMD_transcript_variant		1
TAFA2	ENST00000551619.5	c.-130+41684T>C		intron_variant		2		P1
TAFA2	ENST00000552075.5	c.2+41684T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16319 AN: 152116 Hom.: 999 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.107 AC: 16318 AN: 152234 Hom.: 1000 Cov.: 32 AF XY: 0.107 AC XY: 8000 AN XY: 74428

Gnomad4 AFR AF: 0.0676

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.117

Alfa AF: 0.126 Hom.: 1313

Bravo AF: 0.106

Asia WGS AF: 0.0790 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.6
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11615916; hg19: chr12-62610860;