rs3748841

Variant names:

• chr1-42497129-A-T
• rs3748841
• NM_001395517.1:c.273A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395517.1(CCDC30):​c.273A>T​(p.Gln91His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,232,682 control chromosomes in the GnomAD database, including 15,020 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1550 hom., cov: 32)
  • Exomes 𝑓: 0.16 (13470 hom.)
• Consequence: CCDC30 NM_001395517.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 4 publications found

Genes affected

CCDC30 (HGNC:26103): (coiled-coil domain containing 30)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.002275467).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC30	NM_001395517.1	c.273A>T	p.Gln91His	missense_variant	Exon 5 of 21	ENST00000657597.2	NP_001382446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC30	ENST00000657597.2	c.273A>T	p.Gln91His	missense_variant	Exon 5 of 21		NM_001395517.1	ENSP00000499662.2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20704 AN: 152112 Hom.: 1553 Cov.: 32

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.157 AC: 169430 AN: 1080452 Hom.: 13470 Cov.: 30 AF XY: 0.156 AC XY: 79746 AN XY: 510128

African (AFR) AF: 0.0888 AC: 2044 AN: 23028

American (AMR) AF: 0.158 AC: 1331 AN: 8424

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 2830 AN: 14378

East Asian (EAS) AF: 0.167 AC: 4430 AN: 26508

South Asian (SAS) AF: 0.115 AC: 2249 AN: 19572

European-Finnish (FIN) AF: 0.113 AC: 2432 AN: 21526

Middle Eastern (MID) AF: 0.150 AC: 684 AN: 4546

European-Non Finnish (NFE) AF: 0.160 AC: 146532 AN: 918648

Other (OTH) AF: 0.157 AC: 6898 AN: 43822

GnomAD4 genome AF: 0.136 AC: 20705 AN: 152230 Hom.: 1550 Cov.: 32 AF XY: 0.133 AC XY: 9896 AN XY: 74420

African (AFR) AF: 0.0900 AC: 3739 AN: 41530

American (AMR) AF: 0.155 AC: 2368 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 730 AN: 3472

East Asian (EAS) AF: 0.184 AC: 953 AN: 5176

South Asian (SAS) AF: 0.115 AC: 554 AN: 4830

European-Finnish (FIN) AF: 0.106 AC: 1124 AN: 10604

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10791 AN: 68014

Other (OTH) AF: 0.155 AC: 328 AN: 2114

Alfa AF: 0.147 Hom.: 247

Bravo AF: 0.143

TwinsUK AF: 0.160 AC: 594

ALSPAC AF: 0.165 AC: 636

Asia WGS AF: 0.139 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.5
DANN	Benign	0.78
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0023	T
PhyloP100		-0.36
GERP RS		-1.9
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3748841; hg19: chr1-42962800;