rs200177207

Variant names:

• chr4-69939191-A-C
• rs200177207
• NM_001890.2:c.259A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-69939191-A-C
• chr4-69939191-A-G
• chr4-69939191-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001890.2(CSN1S1):​c.259A>C​(p.Ile87Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I87V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSN1S1 NM_001890.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 4 publications found

Genes affected

CSN1S1 (HGNC:2445): (casein alpha s1) Predicted to be involved in response to dehydroepiandrosterone; response to estradiol; and response to steroid hormone. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07935217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSN1S1	NM_001890.2	c.259A>C	p.Ile87Leu	missense_variant	Exon 10 of 16	ENST00000246891.9	NP_001881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSN1S1	ENST00000246891.9	c.259A>C	p.Ile87Leu	missense_variant	Exon 10 of 16	1	NM_001890.2	ENSP00000246891.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.27
DEOGEN2	Benign	0.066	T;.;.;T;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.38	T;T;T;T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.079	T;T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L;.;.;.;.;.
PhyloP100		3.7
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.78	N;N;N;N;.;N
REVEL	Benign	0.11
Sift	Benign	0.15	T;T;T;T;.;T
Sift4G	Benign	0.46	T;T;T;T;T;T
Polyphen		0.23	B;.;B;.;.;.
Vest4		0.21
MutPred		0.17		Gain of relative solvent accessibility (P = 0.1571);.;Gain of relative solvent accessibility (P = 0.1571);.;.;.;
MVP		0.29
MPC		0.035
ClinPred		0.19	T
GERP RS		5.1
PromoterAI		-0.011	Neutral
Varity_R		0.12
gMVP		0.013

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: rs200177207; hg19: chr4-70804909;