rs12508842

Positions:

• chr4-91096349-T-C
• chr4-91096349-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145065.2(CCSER1):​c.2217+10355T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,994 control chromosomes in the GnomAD database, including 14,698 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 0.43 (14698 hom., cov: 32)
• Consequence: CCSER1 NM_001145065.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16

Genes affected

CCSER1 (HGNC:29349): (coiled-coil serine rich protein 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCSER1	NM_001145065.2	c.2217+10355T>C		intron_variant		ENST00000509176.6	NP_001138537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCSER1	ENST00000509176.6	c.2217+10355T>C		intron_variant		1	NM_001145065.2	ENSP00000425040	P1
CCSER1	ENST00000509109.5	c.*476+10355T>C		intron_variant, NMD_transcript_variant		1		ENSP00000421693
CCSER1	ENST00000649522.1	c.45+10355T>C		intron_variant				ENSP00000497818

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64972 AN: 151878 Hom.: 14700 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.428 AC: 64980 AN: 151994 Hom.: 14698 Cov.: 32 AF XY: 0.430 AC XY: 31910 AN XY: 74278

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.458

Alfa AF: 0.455 Hom.: 20417

Bravo AF: 0.424

Asia WGS AF: 0.576 AC: 2005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12508842; hg19: chr4-92017500;