rs133496

Variant names:

• chr22-48518857-C-T
• rs133496
• NM_001082967.3:c.112+29153C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082967.3(TAFA5):​c.112+29153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,194 control chromosomes in the GnomAD database, including 47,317 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 (47317 hom., cov: 34)
• Consequence: TAFA5 NM_001082967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.112+29153C>T		intron_variant	Intron 1 of 3	ENST00000402357.6	NP_001076436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000402357.6	c.112+29153C>T		intron_variant	Intron 1 of 3	1	NM_001082967.3	ENSP00000383933.2
TAFA5	ENST00000336769.9	c.112+29153C>T		intron_variant	Intron 1 of 3	4		ENSP00000336812.5

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119090 AN: 152076 Hom.: 47302 Cov.: 34

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.898

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.806

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

GnomAD4 genome AF: 0.783 AC: 119149 AN: 152194 Hom.: 47317 Cov.: 34 AF XY: 0.779 AC XY: 57952 AN XY: 74416

African (AFR) AF: 0.672 AC: 27886 AN: 41504

American (AMR) AF: 0.698 AC: 10676 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3175 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3570 AN: 5150

South Asian (SAS) AF: 0.779 AC: 3756 AN: 4824

European-Finnish (FIN) AF: 0.846 AC: 8975 AN: 10612

Middle Eastern (MID) AF: 0.908 AC: 265 AN: 292

European-Non Finnish (NFE) AF: 0.857 AC: 58274 AN: 68012

Other (OTH) AF: 0.807 AC: 1706 AN: 2114

Alfa AF: 0.816 Hom.: 94391

Bravo AF: 0.765

Asia WGS AF: 0.721 AC: 2512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.099
DANN	Benign	0.37
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs133496; hg19: chr22-48914669; COSMIC: COSV60973667;