rs771114454

Variant names:

• chr4-69934236-C-A
• NM_001890.2:c.76C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-69934236-C-A
• chr4-69934236-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001890.2(CSN1S1):​c.76C>A​(p.Arg26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CSN1S1 NM_001890.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03331551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSN1S1	NM_001890.2	c.76C>A	p.Arg26Ser	missense_variant	Exon 3 of 16	ENST00000246891.9	NP_001881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSN1S1	ENST00000246891.9	c.76C>A	p.Arg26Ser	missense_variant	Exon 3 of 16	1	NM_001890.2	ENSP00000246891.4
CSN1S1	ENST00000507772.5	c.76C>A	p.Arg26Ser	missense_variant	Exon 2 of 14	5		ENSP00000427490.1
CSN1S1	ENST00000507763.5	c.76C>A	p.Arg26Ser	missense_variant	Exon 2 of 14	5		ENSP00000422611.1
CSN1S1	ENST00000505782.5	c.76C>A	p.Arg26Ser	missense_variant	Exon 2 of 13	5		ENSP00000426684.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458616 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725656

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0050
DANN	Benign	0.41
DEOGEN2	Benign	0.018	T;.;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.46	T;T;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.033	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.84	N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.84	T;T;T;T
Polyphen		0.041	B;.;B;.
Vest4		0.074
MutPred		0.25		Gain of phosphorylation at R26 (P = 0.0169);Gain of phosphorylation at R26 (P = 0.0169);Gain of phosphorylation at R26 (P = 0.0169);Gain of phosphorylation at R26 (P = 0.0169);
MVP		0.061
MPC		0.036
ClinPred		0.091	T
GERP RS		-2.9
Varity_R		0.062
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-70799954; COSMIC: COSV55892440; COSMIC: COSV55892440;