22-48673638-T-C

Variant names:

• chr22-48673638-T-C
• rs5771934
• NM_001082967.3:c.262+26892T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-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 rank	MANE	Protein	UniProt
TAFA5	NM_001082967.3	c.262+26892T>C		intron_variant	Intron 2 of 3	ENST00000402357.6	NP_001076436.1
TAFA5	NM_015381.7	c.241+26892T>C		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+26892T>C		intron_variant	Intron 2 of 3	1	NM_001082967.3	ENSP00000383933.2
TAFA5	ENST00000336769.9	c.262+26892T>C		intron_variant	Intron 2 of 3	4		ENSP00000336812.5
TAFA5	ENST00000358295.9	c.241+26892T>C		intron_variant	Intron 2 of 3	2		ENSP00000351043.5
TAFA5	ENST00000473898.1	n.120-34079T>C		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.962 AC: 39965 AN: 41540

American (AMR) AF: 0.874 AC: 13361 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2674 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5169 AN: 5174

South Asian (SAS) AF: 0.892 AC: 4294 AN: 4814

European-Finnish (FIN) AF: 0.824 AC: 8734 AN: 10596

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53873 AN: 67994

Other (OTH) AF: 0.856 AC: 1812 AN: 2116

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5771934; hg19: chr22-49069450;