22-48533757-A-G

Position:

• chr22-48533757-A-G

Variant summary

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

The NM_001082967.3(TAFA5):​c.112+44053A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,792 control chromosomes in the GnomAD database, including 9,988 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 0.36 (9988 hom., cov: 33)
• Consequence: TAFA5 NM_001082967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.112+44053A>G		intron_variant		ENST00000402357.6	NP_001076436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000402357.6	c.112+44053A>G		intron_variant		1	NM_001082967.3	ENSP00000383933.2
TAFA5	ENST00000336769.9	c.112+44053A>G		intron_variant		4		ENSP00000336812.5

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54503 AN: 151676 Hom.: 9982 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.359 AC: 54551 AN: 151792 Hom.: 9988 Cov.: 33 AF XY: 0.357 AC XY: 26494 AN XY: 74172

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.358

Alfa AF: 0.381 Hom.: 4943

Bravo AF: 0.343

Asia WGS AF: 0.298 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5768709; hg19: chr22-48929569; COSMIC: COSV60968605;