rs10516889

Positions:

• chr4-91286392-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.2217+200398A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 151,918 control chromosomes in the GnomAD database, including 208 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 0.027 (208 hom., cov: 32)
• Consequence: CCSER1 NM_001145065.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

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

LOC124900733 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCSER1	NM_001145065.2	c.2217+200398A>G		intron_variant		ENST00000509176.6
LOC124900733	XR_007058191.1	n.16421+13620T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCSER1	ENST00000509176.6	c.2217+200398A>G		intron_variant		1	NM_001145065.2	P1
CCSER1	ENST00000649522.1	c.91+2538A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4061 AN: 151800 Hom.: 208 Cov.: 32

Gnomad AFR AF: 0.00565

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0279

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

GnomAD4 genome AF: 0.0267 AC: 4061 AN: 151918 Hom.: 208 Cov.: 32 AF XY: 0.0304 AC XY: 2257 AN XY: 74230

Gnomad4 AFR AF: 0.00566

Gnomad4 AMR AF: 0.0722

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0434

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0141 Hom.: 30

Bravo AF: 0.0291

Asia WGS AF: 0.133 AC: 464 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.75

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: rs10516889; hg19: chr4-92207543;