rs28645201

Positions:

• chr4-90607776-A-G

Variant summary

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

The NM_001145065.2(CCSER1):​c.1725-20249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,262 control chromosomes in the GnomAD database, including 453 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 0.040 (453 hom., cov: 32)
• Consequence: CCSER1 NM_001145065.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCSER1	NM_001145065.2	c.1725-20249A>G		intron_variant		ENST00000509176.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCSER1	ENST00000509176.6	c.1725-20249A>G		intron_variant		1	NM_001145065.2	P1
CCSER1	ENST00000432775.6	c.1725-20249A>G		intron_variant		1
CCSER1	ENST00000505073.5	c.1725-20249A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6126 AN: 152144 Hom.: 452 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0890

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0476

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

GnomAD4 genome AF: 0.0402 AC: 6127 AN: 152262 Hom.: 453 Cov.: 32 AF XY: 0.0439 AC XY: 3268 AN XY: 74456

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0526

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0890

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0480

Alfa AF: 0.0293 Hom.: 19

Bravo AF: 0.0396

Asia WGS AF: 0.184 AC: 638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.78

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: rs28645201; hg19: chr4-91528927;