22-48533757-A-G

Variant names:

• chr22-48533757-A-G
• rs5768709
• NM_001082967.3:c.112+44053A>G

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+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
• Publications: 34 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=-0.99).
• 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 rank	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.112+44053A>G		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+44053A>G		intron_variant	Intron 1 of 3	1	NM_001082967.3	ENSP00000383933.2
TAFA5	ENST00000336769.9	c.112+44053A>G		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.323 AC: 13365 AN: 41384

American (AMR) AF: 0.288 AC: 4404 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1503 AN: 3466

East Asian (EAS) AF: 0.242 AC: 1243 AN: 5142

South Asian (SAS) AF: 0.370 AC: 1778 AN: 4806

European-Finnish (FIN) AF: 0.406 AC: 4267 AN: 10506

Middle Eastern (MID) AF: 0.472 AC: 137 AN: 290

European-Non Finnish (NFE) AF: 0.394 AC: 26783 AN: 67898

Other (OTH) AF: 0.358 AC: 753 AN: 2106

Alfa AF: 0.381 Hom.: 25854

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
PhyloP100		-1.3
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: rs5768709; hg19: chr22-48929569;