chr10-44385008-C-CGCGG

Variant names:

• chr10-44385008-C-CGCGG
• rs76444314
• NM_199168.4:c.-7_-4dupCCGC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_199168.4(CXCL12):​c.-7_-4dupCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00422 in 412,500 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0058 (1 hom., cov: 28)
  • Exomes 𝑓: 0.0036 (2 hom.)
• Consequence: CXCL12 NM_199168.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689
• Publications: 0 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]

ENSG00000303087 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199168.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	NM_199168.4	MANE Select	c.-7_-4dupCCGC		5_prime_UTR	Exon 1 of 3	NP_954637.1
	CXCL12	NM_001178134.2		c.-7_-4dupCCGC		5_prime_UTR	Exon 1 of 4	NP_001171605.1
	CXCL12	NM_001033886.2		c.-7_-4dupCCGC		5_prime_UTR	Exon 1 of 4	NP_001029058.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000343575.11	TSL:1 MANE Select	c.-7_-4dupCCGC		5_prime_UTR	Exon 1 of 3	ENSP00000339913.6
	CXCL12	ENST00000395794.2	TSL:1	c.-7_-4dupCCGC		5_prime_UTR	Exon 1 of 4	ENSP00000379140.2
	CXCL12	ENST00000374426.6	TSL:1	c.-7_-4dupCCGC		5_prime_UTR	Exon 1 of 4	ENSP00000363548.2

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 697 AN: 119510 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00904

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00294

Gnomad FIN AF: 0.000184

Gnomad MID AF: 0.00368

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.00677

GnomAD2 exomes AF: 0.00137 AC: 78 AN: 57116 AF XY: 0.00142

Gnomad AFR exome AF: 0.00325

Gnomad AMR exome AF: 0.00114

Gnomad ASJ exome AF: 0.00611

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.00128

GnomAD4 exome AF: 0.00357 AC: 1045 AN: 292958 Hom.: 2 Cov.: 32 AF XY: 0.00369 AC XY: 591 AN XY: 160248

African (AFR) AF: 0.0110 AC: 85 AN: 7742

American (AMR) AF: 0.00152 AC: 21 AN: 13854

Ashkenazi Jewish (ASJ) AF: 0.0148 AC: 131 AN: 8868

East Asian (EAS) AF: 0.000935 AC: 3 AN: 3210

South Asian (SAS) AF: 0.00101 AC: 42 AN: 41460

European-Finnish (FIN) AF: 0.00151 AC: 15 AN: 9954

Middle Eastern (MID) AF: 0.00454 AC: 5 AN: 1102

European-Non Finnish (NFE) AF: 0.00343 AC: 665 AN: 193976

Other (OTH) AF: 0.00610 AC: 78 AN: 12792

GnomAD4 genome AF: 0.00581 AC: 695 AN: 119542 Hom.: 1 Cov.: 28 AF XY: 0.00537 AC XY: 307 AN XY: 57158

African (AFR) AF: 0.0129 AC: 423 AN: 32862

American (AMR) AF: 0.00366 AC: 42 AN: 11470

Ashkenazi Jewish (ASJ) AF: 0.00904 AC: 28 AN: 3098

East Asian (EAS) AF: 0.00 AC: 0 AN: 3408

South Asian (SAS) AF: 0.00294 AC: 9 AN: 3066

European-Finnish (FIN) AF: 0.000184 AC: 1 AN: 5434

Middle Eastern (MID) AF: 0.00407 AC: 1 AN: 246

European-Non Finnish (NFE) AF: 0.00313 AC: 180 AN: 57556

Other (OTH) AF: 0.00671 AC: 11 AN: 1640

Alfa AF: 0.0000563 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
Mutation Taster		=299/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs76444314; hg19: chr10-44880456;