1-112721089-C-T

Position:

• chr1-112721089-C-T

Variant summary

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

The ENST00000361886.4(TAFA3):​c.-2+455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,016 control chromosomes in the GnomAD database, including 17,278 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 0.47 (17278 hom., cov: 32)
• Consequence: TAFA3 ENST00000361886.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

Genes affected

TAFA3 (HGNC:21590): (TAFA chemokine like family member 3) 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 encoding multiple isoforms 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAFA3	NM_182759.3	c.-2+455C>T		intron_variant		ENST00000361886.4	NP_877436.1
TAFA3	NM_001004440.2	c.-2+455C>T		intron_variant			NP_001004440.1
TAFA3	NR_169586.1	n.453+455C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFA3	ENST00000361886.4	c.-2+455C>T		intron_variant		1	NM_182759.3	ENSP00000355042	P1
TAFA3	ENST00000369630.7	c.-2+455C>T		intron_variant		1		ENSP00000358644

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71758 AN: 151898 Hom.: 17261 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.473 AC: 71834 AN: 152016 Hom.: 17278 Cov.: 32 AF XY: 0.467 AC XY: 34668 AN XY: 74288

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.510

Alfa AF: 0.490 Hom.: 36133

Bravo AF: 0.482

Asia WGS AF: 0.469 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.3
DANN	Benign	0.52

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: rs4450019; hg19: chr1-113263711;