rs4128705

Variant names:

• chr4-91362620-T-G
• rs4128705
• NM_001145065.2:c.2218-235952T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145065.2(CCSER1):​c.2218-235952T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,680 control chromosomes in the GnomAD database, including 6,867 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 0.28 (6867 hom., cov: 32)
• Consequence: CCSER1 NM_001145065.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSER1	NM_001145065.2	c.2218-235952T>G		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.2218-235952T>G		intron_variant	Intron 10 of 10	1	NM_001145065.2	ENSP00000425040.1
CCSER1	ENST00000649522.1	c.91+78766T>G		intron_variant	Intron 2 of 2			ENSP00000497818.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42827 AN: 151562 Hom.: 6858 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.283 AC: 42866 AN: 151680 Hom.: 6867 Cov.: 32 AF XY: 0.274 AC XY: 20347 AN XY: 74126

African (AFR) AF: 0.288 AC: 11934 AN: 41436

American (AMR) AF: 0.263 AC: 3998 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1400 AN: 3466

East Asian (EAS) AF: 0.0763 AC: 395 AN: 5176

South Asian (SAS) AF: 0.204 AC: 986 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2197 AN: 10552

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.308 AC: 20879 AN: 67730

Other (OTH) AF: 0.314 AC: 660 AN: 2100

Alfa AF: 0.310 Hom.: 7182

Bravo AF: 0.289

Asia WGS AF: 0.168 AC: 581 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.75
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism (auto)

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: rs4128705; hg19: chr4-92283771;