chr10-44378544-C-CCT

Variant names:

• chr10-44378544-C-CCT
• rs2839694
• NM_199168.4:c.*87_*88dupAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_199168.4(CXCL12):​c.*87_*88dupAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,596,194 control chromosomes in the GnomAD database, including 56,097 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4623 hom., cov: 26)
  • Exomes 𝑓: 0.26 (51474 hom.)
• Consequence: CXCL12 NM_199168.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.46
• Publications: 3 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 -10 ACMG points.

• BP6: Variant 10-44378544-C-CCT is Benign according to our data. Variant chr10-44378544-C-CCT is described in ClinVar as Benign. ClinVar VariationId is 1274726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	NM_199168.4	MANE Select	c.*87_*88dupAG		3_prime_UTR	Exon 3 of 3	NP_954637.1	P48061-2
	CXCL12	NM_001178134.2		c.266+91_266+92dupAG		intron	N/A	NP_001171605.1	P48061-4
	CXCL12	NM_001033886.2		c.266+91_266+92dupAG		intron	N/A	NP_001029058.1	P48061-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000343575.11	TSL:1 MANE Select	c.*87_*88dupAG		3_prime_UTR	Exon 3 of 3	ENSP00000339913.6	P48061-2
	CXCL12	ENST00000395794.2	TSL:1	c.266+91_266+92dupAG		intron	N/A	ENSP00000379140.2	P48061-4
	CXCL12	ENST00000374426.6	TSL:1	c.266+91_266+92dupAG		intron	N/A	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34039 AN: 151916 Hom.: 4622 Cov.: 26

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.260 AC: 375834 AN: 1444160 Hom.: 51474 Cov.: 34 AF XY: 0.258 AC XY: 185276 AN XY: 716924

African (AFR) AF: 0.0747 AC: 2480 AN: 33180

American (AMR) AF: 0.474 AC: 20350 AN: 42904

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6045 AN: 25446

East Asian (EAS) AF: 0.138 AC: 5447 AN: 39336

South Asian (SAS) AF: 0.234 AC: 19704 AN: 84208

European-Finnish (FIN) AF: 0.323 AC: 16773 AN: 51912

Middle Eastern (MID) AF: 0.184 AC: 1046 AN: 5698

European-Non Finnish (NFE) AF: 0.263 AC: 289503 AN: 1101866

Other (OTH) AF: 0.243 AC: 14486 AN: 59610

GnomAD4 genome AF: 0.224 AC: 34042 AN: 152034 Hom.: 4623 Cov.: 26 AF XY: 0.231 AC XY: 17138 AN XY: 74294

African (AFR) AF: 0.0850 AC: 3531 AN: 41540

American (AMR) AF: 0.390 AC: 5938 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3468

East Asian (EAS) AF: 0.138 AC: 711 AN: 5160

South Asian (SAS) AF: 0.220 AC: 1059 AN: 4814

European-Finnish (FIN) AF: 0.339 AC: 3578 AN: 10546

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17571 AN: 67952

Other (OTH) AF: 0.250 AC: 527 AN: 2112

Alfa AF: 0.241 Hom.: 605

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2839694; hg19: chr10-44873992; COSMIC: COSV59106998; COSMIC: COSV59106998;