NM_001145065.2:c.2217+105998T>C

Variant names:

• chr4-91191992-T-C
• rs10516888
• NM_001145065.2:c.2217+105998T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001145065.2(CCSER1):​c.2217+105998T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 152,322 control chromosomes in the GnomAD database, including 58 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 0.017 (58 hom., cov: 32)
• Consequence: CCSER1 NM_001145065.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0171 (2607/152322) while in subpopulation AFR AF = 0.0503 (2090/41566). AF 95% confidence interval is 0.0485. There are 58 homozygotes in GnomAd4. There are 1241 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSER1	NM_001145065.2	c.2217+105998T>C		intron_variant	Intron 10 of 10	ENST00000509176.6	NP_001138537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCSER1	ENST00000509176.6	c.2217+105998T>C		intron_variant	Intron 10 of 10	1	NM_001145065.2	ENSP00000425040.1
CCSER1	ENST00000649522.1	c.46-91817T>C		intron_variant	Intron 1 of 2			ENSP00000497818.1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2598 AN: 152204 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00431

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0171 AC: 2607 AN: 152322 Hom.: 58 Cov.: 32 AF XY: 0.0167 AC XY: 1241 AN XY: 74504

African (AFR) AF: 0.0503 AC: 2090 AN: 41566

American (AMR) AF: 0.0112 AC: 172 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10630

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00431 AC: 293 AN: 68020

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.0105 Hom.: 7

Bravo AF: 0.0200

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.0
DANN	Benign	0.54
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10516888; hg19: chr4-92113143;