rs771142191

Variant names:

• chr7-105565262-A-G
• rs771142191
• NM_001355526.2:c.*185T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001355526.2(EFCAB10):​c.*185T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000899 in 1,558,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: EFCAB10 NM_001355526.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.14
• Publications: 1 publications found

Genes affected

EFCAB10 (HGNC:34531): (EF-hand calcium binding domain 10) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

RINT1 (HGNC:21876): (RAD50 interactor 1) This gene encodes a protein first identified for its ability to interact with the RAD50 double strand break repair protein, with the resulting interaction implicated in the regulation of cell cycle progression and telomere length. The encoded protein may also play a role in trafficking of cellular cargo from the endosome to the trans-Golgi network. Mutations in this gene may be associated with breast cancer in human patients. [provided by RefSeq, Oct 2016]

RINT1 Gene-Disease associations (from GenCC):

• infantile liver failure syndrome 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• infantile liver failure syndrome 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355526.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB10	NM_001355526.2	MANE Select	c.*185T>C		3_prime_UTR	Exon 5 of 5	NP_001342455.1	A6NFE3
	RINT1	NM_021930.6	MANE Select	c.1887-15A>G		intron	N/A	NP_068749.3
	EFCAB10	NM_001355530.2		c.*287T>C		3_prime_UTR	Exon 5 of 5	NP_001342459.1	J3KR52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB10	ENST00000480514.6	TSL:1 MANE Select	c.*185T>C		3_prime_UTR	Exon 5 of 5	ENSP00000418678.1	A6NFE3
	RINT1	ENST00000257700.7	TSL:1 MANE Select	c.1887-15A>G		intron	N/A	ENSP00000257700.2	Q6NUQ1
	EFCAB10	ENST00000485614.5	TSL:5	c.*287T>C		3_prime_UTR	Exon 5 of 5	ENSP00000417841.1	J3KR52

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000462 AC: 1 AN: 216662 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000959

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000782 AC: 11 AN: 1405796 Hom.: 0 Cov.: 30 AF XY: 0.00000865 AC XY: 6 AN XY: 694016

African (AFR) AF: 0.0000325 AC: 1 AN: 30774

American (AMR) AF: 0.00 AC: 0 AN: 32298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23676

East Asian (EAS) AF: 0.00 AC: 0 AN: 38974

South Asian (SAS) AF: 0.00 AC: 0 AN: 79122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 0.00000921 AC: 10 AN: 1085330

Other (OTH) AF: 0.00 AC: 0 AN: 57712

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.0000724 AC: 3 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5208

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.66
DANN	Benign	0.77
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.58		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.58		Position offset: 1

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

Other links and lift over

dbSNP: rs771142191; hg19: chr7-105205709; COSMIC: COSV99994252; COSMIC: COSV99994252;