2-158176670-G-A

Variant names:

• chr2-158176670-G-A
• rs764349131
• NM_138803.4:c.1489-9C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_138803.4(CCDC148):​c.1489-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,090 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCDC148 NM_138803.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620
• Publications: 0 publications found

Genes affected

CCDC148 (HGNC:25191): (coiled-coil domain containing 148)

CCDC148-AS1 (HGNC:44134): (CCDC148 antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-158176670-G-A is Benign according to our data. Variant chr2-158176670-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 761064.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138803.4. 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
	CCDC148	NM_138803.4	MANE Select	c.1489-9C>T		intron	N/A	NP_620158.3
	CCDC148	NM_001301684.2		c.1051-9C>T		intron	N/A	NP_001288613.1
	CCDC148-AS1	NR_038850.1		n.144G>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC148	ENST00000283233.10	TSL:1 MANE Select	c.1489-9C>T		intron	N/A	ENSP00000283233.5	Q8NFR7-1
	CCDC148-AS1	ENST00000412781.2	TSL:1	n.144G>A		non_coding_transcript_exon	Exon 2 of 5
	CCDC148	ENST00000448656.5	TSL:1	n.*1080-9C>T		intron	N/A	ENSP00000415540.1	F8WCV9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459090 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725870

⚠️ 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: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39352

South Asian (SAS) AF: 0.00 AC: 0 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110550

Other (OTH) AF: 0.00 AC: 0 AN: 60218

⚠️ 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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	-0.81
CADD	Benign	5.7
DANN	Benign	0.68
PhyloP100		-0.062

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: rs764349131; hg19: chr2-159033182;