Genetic Variant EFCAB5:c.2365+535A>G (chr17-30056691-A-G) – ACMG Classification: Benign (-12 pts)

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong

The NM_198529.4(EFCAB5):c.2365+535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.167 (AC=25,489) in the gnomAD database across 152,212 control chromosomes, including 2,827 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.239. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2827 hom., cov: 32)

Consequence

EFCAB5
NM_198529.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.398

Publications

9 publications found

Variant links:

Genes affected

EFCAB5 (HGNC:24801): (EF-hand calcium binding domain 5) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

EFCAB5 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_198529.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2393 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198529.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFCAB5	NM_198529.4	MANE Select	c.2365+535A>G	intron	N/A	NP_940931.3	A4FU69-1
EFCAB5	NM_001145053.2		c.2197+535A>G	intron	N/A	NP_001138525.2	A4FU69-5
EFCAB5	NR_026738.2		n.2528+535A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EFCAB5	ENST00000394835.8	TSL:1 MANE Select	c.2365+535A>G	intron	N/A	ENSP00000378312.3	A4FU69-1
EFCAB5	ENST00000588978.1	TSL:1	c.1759+535A>G	intron	N/A	ENSP00000465109.1	K7EJC3
EFCAB5	ENST00000440741.7	TSL:1	n.2365+535A>G	intron	N/A	ENSP00000393095.2	A4FU69-2

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25486

AN:

152094

Hom.:

2824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0478

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.0298

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.169

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

GnomAD4 genome

AF:

0.167

AC:

25489

AN:

152212

Hom.:

2827

Cov.:

AF XY:

0.162

AC XY:

12091

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0476

AC:

1980

AN:

41566

American (AMR)

AF:

0.162

AC:

2469

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

684

AN:

3470

East Asian (EAS)

AF:

0.0297

AC:

154

AN:

5186

South Asian (SAS)

AF:

0.112

AC:

543

AN:

4832

European-Finnish (FIN)

AF:

0.239

AC:

2531

AN:

10584

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16477

AN:

67976

Other (OTH)

AF:

0.167

AC:

352

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1042

2084

3126

4168

5210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.220

Hom.:

6035

Bravo

AF:

0.158

Asia WGS

AF:

0.0670

AC:

232

AN:

3476

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.0328

AC:

3993

AN:

121910

Turkish Variome

AF:

0.173

AC:

268

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.0358

AC:

321

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.180

AC:

422

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over