17-47347749-G-C

Variant names:

• chr17-47347749-G-C
• rs7206971
• NM_152347.5:c.518-59G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001426591.1(EFCAB13):​c.*2634G>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 0.000000913 in 1,095,634 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: EFCAB13 NM_001426591.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 0 publications found

Genes affected

EFCAB13 (HGNC:26864): (EF-hand calcium binding domain 13)

EFCAB13-DT (HGNC:55338): (EFCAB13 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001426591.1. 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
	EFCAB13	NM_152347.5	MANE Select	c.518-59G>C		intron	N/A	NP_689560.3
	EFCAB13	NM_001426591.1		c.*2634G>C		3_prime_UTR	Exon 8 of 8	NP_001413520.1
	EFCAB13	NM_001426592.1		c.*2634G>C		3_prime_UTR	Exon 7 of 7	NP_001413521.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFCAB13	ENST00000331493.7	TSL:1 MANE Select	c.518-59G>C		intron	N/A	ENSP00000332111.2	Q8IY85-1
	EFCAB13	ENST00000517484.5	TSL:2	c.517+2651G>C		intron	N/A	ENSP00000430048.1	Q8IY85-2
	EFCAB13	ENST00000517310.5	TSL:2	c.73+2651G>C		intron	N/A	ENSP00000466136.1	K7ELL9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095634 Hom.: 0 AF XY: 0.00000189 AC XY: 1 AN XY: 530268

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23580

American (AMR) AF: 0.00 AC: 0 AN: 19674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16742

East Asian (EAS) AF: 0.00 AC: 0 AN: 30560

South Asian (SAS) AF: 0.00 AC: 0 AN: 29444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4138

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 888522

Other (OTH) AF: 0.00 AC: 0 AN: 44424

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.50
PhyloP100		-1.2

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: rs7206971; hg19: chr17-45425115;