rs2079821130

Variant names:

• chr3-58867813-A-C
• rs2079821130
• NM_001394063.1:c.1135+4T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001394063.1(CFAP20DC):​c.1135+4T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFAP20DC NM_001394063.1 splice_region, intron
• Scores: Splicing: ADA: 0.0003144
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0250
• Publications: 0 publications found

Genes affected

CFAP20DC (HGNC:24763): (CFAP20 domain containing)

CFAP20DC-AS1 (HGNC:41063): (CFAP20DC antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 3-58867813-A-C is Benign according to our data. Variant chr3-58867813-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2653922.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394063.1. 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
	CFAP20DC	NM_001394063.1	MANE Select	c.1135+4T>G		splice_region intron	N/A	NP_001380992.1	A0A2U3TZK7
	CFAP20DC	NM_001351530.2		c.970+4T>G		splice_region intron	N/A	NP_001338459.1
	CFAP20DC	NM_001351531.2		c.520+4T>G		splice_region intron	N/A	NP_001338460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP20DC	ENST00000482387.7	TSL:5 MANE Select	c.1135+4T>G		splice_region intron	N/A	ENSP00000417122.2	A0A2U3TZK7
	CFAP20DC	ENST00000468415.6	TSL:1	n.*565+4T>G		splice_region intron	N/A	ENSP00000419142.2	F8WF72
	CFAP20DC	ENST00000938702.1		c.1132+4T>G		splice_region intron	N/A	ENSP00000608761.1

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.000625

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00413 AC: 5964 AN: 1444996 Hom.: 0 Cov.: 30 AF XY: 0.00395 AC XY: 2843 AN XY: 719450

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

African (AFR) AF: 0.00326 AC: 108 AN: 33146

American (AMR) AF: 0.000627 AC: 28 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00270 AC: 70 AN: 25964

East Asian (EAS) AF: 0.00284 AC: 112 AN: 39454

South Asian (SAS) AF: 0.00136 AC: 117 AN: 85954

European-Finnish (FIN) AF: 0.00152 AC: 81 AN: 53236

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5746

European-Non Finnish (NFE) AF: 0.00473 AC: 5192 AN: 1097010

Other (OTH) AF: 0.00401 AC: 240 AN: 59822

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000243 AC: 37 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74378

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

African (AFR) AF: 0.0000962 AC: 4 AN: 41560

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5164

South Asian (SAS) AF: 0.000626 AC: 3 AN: 4796

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.44
CADD	Benign	9.3
DANN	Benign	0.74
PhyloP100		0.025
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.13
SpliceAI score (max)		0.090		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: rs2079821130; hg19: chr3-58853539; COSMIC: COSV108098655;