22-48673638-T-C

Position:

• chr22-48673638-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.262+26892T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 152,198 control chromosomes in the GnomAD database, including 56,862 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 0.86 (56862 hom., cov: 32)
• Consequence: TAFA5 NM_001082967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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]

TAFA5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.262+26892T>C		intron_variant		ENST00000402357.6	NP_001076436.1
TAFA5	NM_015381.7	c.241+26892T>C		intron_variant			NP_056196.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000402357.6	c.262+26892T>C		intron_variant		1	NM_001082967.3	ENSP00000383933.2
TAFA5	ENST00000336769.9	c.262+26892T>C		intron_variant		4		ENSP00000336812.5
TAFA5	ENST00000358295.9	c.241+26892T>C		intron_variant		2		ENSP00000351043.5
TAFA5	ENST00000473898.1	n.120-34079T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130794 AN: 152080 Hom.: 56796 Cov.: 32

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.860 AC: 130921 AN: 152198 Hom.: 56862 Cov.: 32 AF XY: 0.864 AC XY: 64250 AN XY: 74406

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.874

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.856

Alfa AF: 0.834 Hom.: 6612

Bravo AF: 0.865

Asia WGS AF: 0.939 AC: 3264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.9
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: rs5771934; hg19: chr22-49069450;