chr10-44383265-G-A

Variant names:

• chr10-44383265-G-A
• rs3780891
• NM_199168.4:c.61+1680C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199168.4(CXCL12):​c.61+1680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 152,238 control chromosomes in the GnomAD database, including 487 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 0.075 (487 hom., cov: 32)
• Consequence: CXCL12 NM_199168.4 intron
• Scores: Splicing: ADA: 0.00005694
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.61+1680C>T		intron_variant	Intron 1 of 2	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.61+1680C>T		intron_variant	Intron 1 of 2	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11482 AN: 152120 Hom.: 488 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0677

Gnomad FIN AF: 0.0782

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.0975

GnomAD2 exomes AF: 0.114 AC: 5 AN: 44 AF XY: 0.0625

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.167

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

GnomAD4 genome AF: 0.0754 AC: 11480 AN: 152238 Hom.: 487 Cov.: 32 AF XY: 0.0750 AC XY: 5580 AN XY: 74448

African (AFR) AF: 0.0359 AC: 1490 AN: 41548

American (AMR) AF: 0.0833 AC: 1274 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3468

East Asian (EAS) AF: 0.0951 AC: 492 AN: 5176

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4824

European-Finnish (FIN) AF: 0.0782 AC: 830 AN: 10612

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0967 AC: 6572 AN: 67990

Other (OTH) AF: 0.0965 AC: 204 AN: 2114

Alfa AF: 0.0747 Hom.: 265

Bravo AF: 0.0750

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.27
PhyloP100		-0.061
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs3780891; hg19: chr10-44878713;