22-48672561-G-T

Variant names:

• chr22-48672561-G-T
• rs5771932
• NM_001082967.3:c.262+25815G>T

Variant summary

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

The NM_001082967.3(TAFA5):​c.262+25815G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,082 control chromosomes in the GnomAD database, including 3,413 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 0.21 (3413 hom., cov: 33)
• Consequence: TAFA5 NM_001082967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.262+25815G>T		intron_variant	Intron 2 of 3	ENST00000402357.6	NP_001076436.1
TAFA5	NM_015381.7	c.241+25815G>T		intron_variant	Intron 2 of 3		NP_056196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000402357.6	c.262+25815G>T		intron_variant	Intron 2 of 3	1	NM_001082967.3	ENSP00000383933.2
TAFA5	ENST00000336769.9	c.262+25815G>T		intron_variant	Intron 2 of 3	4		ENSP00000336812.5
TAFA5	ENST00000358295.9	c.241+25815G>T		intron_variant	Intron 2 of 3	2		ENSP00000351043.5
TAFA5	ENST00000473898.1	n.120-35156G>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31806 AN: 151964 Hom.: 3409 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.209 AC: 31833 AN: 152082 Hom.: 3413 Cov.: 33 AF XY: 0.207 AC XY: 15424 AN XY: 74374

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.201

Alfa AF: 0.112 Hom.: 156

Bravo AF: 0.208

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.63

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: rs5771932; hg19: chr22-49068373;