10-44373416-C-T

Position:

• chr10-44373416-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000374429.6(CXCL12):​c.267-73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,349,348 control chromosomes in the GnomAD database, including 1,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (149 hom., cov: 34)
  • Exomes 𝑓: 0.048 (1671 hom.)
• Consequence: CXCL12 ENST00000374429.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.63

Genes affected

CXCL12 (HGNC:10672): (C-X-C motif chemokine ligand 12) This antimicrobial gene encodes a stromal cell-derived alpha chemokine member of the intercrine family. The encoded protein functions as the ligand for the G-protein coupled receptor, chemokine (C-X-C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-44373416-C-T is Benign according to our data. Variant chr10-44373416-C-T is described in ClinVar as [Benign]. Clinvar id is 1237787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_000609.7	c.267-73G>A		intron_variant			NP_000600.1
CXCL12	NM_001277990.2	c.110-326G>A		intron_variant			NP_001264919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.267-73G>A		intron_variant		1		ENSP00000363551	A1
CXCL12	ENST00000395793.7	c.110-326G>A		intron_variant		5		ENSP00000379139

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5932 AN: 152190 Hom.: 151 Cov.: 34

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0480

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0476 AC: 56944 AN: 1197040 Hom.: 1671 AF XY: 0.0502 AC XY: 30263 AN XY: 602506

Gnomad4 AFR exome AF: 0.0222

Gnomad4 AMR exome AF: 0.0221

Gnomad4 ASJ exome AF: 0.0807

Gnomad4 EAS exome AF: 0.000250

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.0460

Gnomad4 OTH exome AF: 0.0472

GnomAD4 genome AF: 0.0390 AC: 5933 AN: 152308 Hom.: 149 Cov.: 34 AF XY: 0.0390 AC XY: 2907 AN XY: 74468

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0988

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0480

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0453 Hom.: 17

Bravo AF: 0.0341

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.044
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266090; hg19: chr10-44868864;