rs7259

Variant names:

• chr9-128434425-G-A
• rs7259
• NM_016174.5:c.1347G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_016174.5(CERCAM):​c.1347G>A​(p.Lys449Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,612,898 control chromosomes in the GnomAD database, including 45,610 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 0.32 (10286 hom., cov: 32)
  • Exomes 𝑓: 0.20 (35324 hom.)
• Consequence: CERCAM NM_016174.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 14 publications found

Genes affected

CERCAM (HGNC:23723): (cerebral endothelial cell adhesion molecule) Enables identical protein binding activity. Acts upstream of or within cell adhesion. Predicted to be located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=1.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERCAM	NM_016174.5	c.1347G>A	p.Lys449Lys	synonymous_variant	Exon 11 of 13	ENST00000372838.9	NP_057258.3
CERCAM	NM_001286760.1	c.1113G>A	p.Lys371Lys	synonymous_variant	Exon 11 of 13		NP_001273689.1
CERCAM	XM_011518763.4	c.1113G>A	p.Lys371Lys	synonymous_variant	Exon 11 of 13		XP_011517065.1
CERCAM	XM_047423450.1	c.1113G>A	p.Lys371Lys	synonymous_variant	Exon 12 of 14		XP_047279406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERCAM	ENST00000372838.9	c.1347G>A	p.Lys449Lys	synonymous_variant	Exon 11 of 13	1	NM_016174.5	ENSP00000361929.4

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48125 AN: 151774 Hom.: 10258 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.248 AC: 62018 AN: 250386 AF XY: 0.239

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.406

Gnomad FIN exome AF: 0.243

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.204 AC: 297917 AN: 1461006 Hom.: 35324 Cov.: 34 AF XY: 0.204 AC XY: 147987 AN XY: 726866

African (AFR) AF: 0.629 AC: 21063 AN: 33468

American (AMR) AF: 0.228 AC: 10199 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3833 AN: 26130

East Asian (EAS) AF: 0.415 AC: 16478 AN: 39692

South Asian (SAS) AF: 0.238 AC: 20499 AN: 86232

European-Finnish (FIN) AF: 0.237 AC: 12594 AN: 53182

Middle Eastern (MID) AF: 0.245 AC: 1407 AN: 5748

European-Non Finnish (NFE) AF: 0.179 AC: 198604 AN: 1111468

Other (OTH) AF: 0.219 AC: 13240 AN: 60374

GnomAD4 genome AF: 0.317 AC: 48208 AN: 151892 Hom.: 10286 Cov.: 32 AF XY: 0.317 AC XY: 23552 AN XY: 74238

African (AFR) AF: 0.613 AC: 25367 AN: 41380

American (AMR) AF: 0.222 AC: 3387 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2055 AN: 5132

South Asian (SAS) AF: 0.251 AC: 1209 AN: 4816

European-Finnish (FIN) AF: 0.245 AC: 2586 AN: 10552

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12366 AN: 67950

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.231 Hom.: 4164

Bravo AF: 0.331

Asia WGS AF: 0.355 AC: 1234 AN: 3478

EpiCase AF: 0.172

EpiControl AF: 0.175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.6
DANN	Benign	0.44
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs7259; hg19: chr9-131196704; COSMIC: COSV65710984; COSMIC: COSV65710984;