4-91484964-A-T

Variant summary

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

The NM_001145065.2(CCSER1):c.2218-113608A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,906 control chromosomes in the GnomAD database, including 26,018 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 0.58 (26018 hom., cov: 32)
• Consequence: CCSER1 NM_001145065.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCSER1	NM_001145065.2	c.2218-113608A>T		intron_variant		ENST00000509176.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCSER1	ENST00000509176.6	c.2218-113608A>T		intron_variant		1	NM_001145065.2	P1
CCSER1	ENST00000649522.1	c.92-113608A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88016 AN: 151790 Hom.: 25996 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.580 AC: 88090 AN: 151906 Hom.: 26018 Cov.: 32 AF XY: 0.584 AC XY: 43338 AN XY: 74230

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.550

Alfa AF: 0.559 Hom.: 2967

Bravo AF: 0.581

Asia WGS AF: 0.723 AC: 2513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.0
Dann	Benign	0.76

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: rs10007512; hg19: chr4-92406115;