22-48688075-T-C

Position:

• chr22-48688075-T-C

Variant summary

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

The NM_001082967.3(TAFA5):​c.263-19642T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 148,994 control chromosomes in the GnomAD database, including 45,860 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 0.78 (45860 hom., cov: 28)
• Consequence: TAFA5 NM_001082967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

Genes affected

TAFA5 (HGNC:21592): (TAFA chemokine like family member 5) 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, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.263-19642T>C		intron_variant		ENST00000402357.6	NP_001076436.1
TAFA5	NM_015381.7	c.242-19642T>C		intron_variant			NP_056196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000402357.6	c.263-19642T>C		intron_variant		1	NM_001082967.3	ENSP00000383933	P4
TAFA5	ENST00000336769.9	c.263-19642T>C		intron_variant		4		ENSP00000336812
TAFA5	ENST00000358295.9	c.242-19642T>C		intron_variant		2		ENSP00000351043	A1
TAFA5	ENST00000473898.1	n.120-19642T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.784 AC: 116698 AN: 148874 Hom.: 45821 Cov.: 28

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.784 AC: 116802 AN: 148994 Hom.: 45860 Cov.: 28 AF XY: 0.780 AC XY: 56609 AN XY: 72542

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.787

Alfa AF: 0.821 Hom.: 60684

Bravo AF: 0.758

Asia WGS AF: 0.658 AC: 2273 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.37

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: rs130110; hg19: chr22-49083887;