chr16-90027670-A-G

Variant names:

• chr16-90027670-A-G
• rs61734732
• NM_001481.3:c.38A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001481.3(DRC4):​c.38A>G​(p.Lys13Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0019 in 1,614,190 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (27 hom.)
• Consequence: DRC4 NM_001481.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.94
• Publications: 2 publications found

Genes affected

DRC4 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

DRC4 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 33

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004105091).
• BP6: Variant 16-90027670-A-G is Benign according to our data. Variant chr16-90027670-A-G is described in ClinVar as Benign. ClinVar VariationId is 475564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1597/152358) while in subpopulation AFR AF = 0.0371 (1544/41586). AF 95% confidence interval is 0.0356. There are 28 homozygotes in GnomAd4. There are 737 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001481.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRC4	NM_001481.3	MANE Select	c.38A>G	p.Lys13Arg	missense	Exon 2 of 11	NP_001472.1
	DRC4	NM_001286209.2		c.-38A>G		5_prime_UTR	Exon 2 of 11	NP_001273138.1
	DRC4	NM_001286205.2		c.-335A>G		5_prime_UTR	Exon 2 of 11	NP_001273134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS8	ENST00000268699.9	TSL:1 MANE Select	c.38A>G	p.Lys13Arg	missense	Exon 2 of 11	ENSP00000268699.4
	GAS8	ENST00000564853.1	TSL:1	n.90A>G		non_coding_transcript_exon	Exon 2 of 2
	GAS8	ENST00000566266.5	TSL:1	n.38A>G		non_coding_transcript_exon	Exon 2 of 10	ENSP00000454343.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1599 AN: 152240 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00248

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00267 AC: 672 AN: 251432 AF XY: 0.00196

Gnomad AFR exome AF: 0.0387

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00101 AC: 1471 AN: 1461832 Hom.: 27 Cov.: 32 AF XY: 0.000861 AC XY: 626 AN XY: 727216

African (AFR) AF: 0.0383 AC: 1281 AN: 33472

American (AMR) AF: 0.00101 AC: 45 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111992

Other (OTH) AF: 0.00190 AC: 115 AN: 60394

GnomAD4 genome AF: 0.0105 AC: 1597 AN: 152358 Hom.: 28 Cov.: 33 AF XY: 0.00989 AC XY: 737 AN XY: 74520

African (AFR) AF: 0.0371 AC: 1544 AN: 41586

American (AMR) AF: 0.00242 AC: 37 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00373 Hom.: 22

Bravo AF: 0.0121

ESP6500AA AF: 0.0348 AC: 153

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00324 AC: 393

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 33 Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.087
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.099
Sift	Benign	0.23	T
Sift4G	Benign	0.31	T
Polyphen		0.35	B
Vest4		0.29
MVP		0.67
MPC		0.017
ClinPred		0.020	T
GERP RS		5.5
Varity_R		0.11
gMVP		0.16
Mutation Taster		=288/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.020		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: rs61734732; hg19: chr16-90094078; COSMIC: COSV99064917; COSMIC: COSV99064917;