3-68755873-T-C

Position:

• chr3-68755873-T-C

Variant summary

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

The NM_182522.5(TAFA4):​c.131-2855A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,116 control chromosomes in the GnomAD database, including 38,479 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 0.71 (38479 hom., cov: 32)
• Consequence: TAFA4 NM_182522.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAFA4	NM_182522.5	c.131-2855A>G		intron_variant		ENST00000295569.12	NP_872328.1
TAFA4	NM_001005527.3	c.131-2855A>G		intron_variant			NP_001005527.1
TAFA4	XM_011533371.2	c.131-2855A>G		intron_variant			XP_011531673.1
TAFA4	XM_011533372.2	c.131-2855A>G		intron_variant			XP_011531674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFA4	ENST00000295569.12	c.131-2855A>G		intron_variant		1	NM_182522.5	ENSP00000295569.7
TAFA4	ENST00000495737.1	c.131-2855A>G		intron_variant		4		ENSP00000419439.1
TAFA4	ENST00000634242.1	c.131-2855A>G		intron_variant		5		ENSP00000489092.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107227 AN: 151998 Hom.: 38454 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.705 AC: 107304 AN: 152116 Hom.: 38479 Cov.: 32 AF XY: 0.710 AC XY: 52787 AN XY: 74352

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.685

Alfa AF: 0.636 Hom.: 5433

Bravo AF: 0.704

Asia WGS AF: 0.883 AC: 3071 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	0.084
DANN	Benign	0.47

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: rs1489992; hg19: chr3-68805024;