12-61992819-A-G

Variant names:

• chr12-61992819-A-G
• rs11174267
• NM_178539.5:c.-1-125393T>C

Variant summary

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

The NM_178539.5(TAFA2):​c.-1-125393T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,128 control chromosomes in the GnomAD database, including 7,259 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 0.29 (7259 hom., cov: 32)
• Consequence: TAFA2 NM_178539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA2	NM_178539.5	c.-1-125393T>C		intron_variant	Intron 1 of 4	ENST00000416284.8	NP_848634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA2	ENST00000416284.8	c.-1-125393T>C		intron_variant	Intron 1 of 4	1	NM_178539.5	ENSP00000393987.3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43398 AN: 152010 Hom.: 7256 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.285 AC: 43398 AN: 152128 Hom.: 7259 Cov.: 32 AF XY: 0.283 AC XY: 21044 AN XY: 74364

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.282

Alfa AF: 0.352 Hom.: 13038

Bravo AF: 0.267

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.34
DANN	Benign	0.68

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: rs11174267; hg19: chr12-62386600;