rs872010

Variant names:

• chr16-90022379-G-A
• rs872010
• NM_001286209.2:c.-73+2611G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-90022379-G-A
• chr16-90022379-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001286209.2(DRC4):​c.-73+2611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,218 control chromosomes in the GnomAD database, including 2,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2849 hom., cov: 33)
• Consequence: DRC4 NM_001286209.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45
• Publications: 5 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), PanelApp Australia, ClinGen, G2P, Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 16-90022379-G-A is Benign according to our data. Variant chr16-90022379-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286209.2. 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
	DRC4	NM_001286209.2		c.-73+2611G>A		intron	N/A	NP_001273138.1	O95995-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS8	ENST00000536122.7	TSL:2	c.-73+2611G>A		intron	N/A	ENSP00000440977.1	O95995-2
	GAS8	ENST00000564392.5	TSL:3	c.-73+173G>A		intron	N/A	ENSP00000455172.1	H3BP65
	GAS8	ENST00000561675.1	TSL:3	c.-269+2611G>A		intron	N/A	ENSP00000457554.1	H3BUA7

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23536 AN: 152102 Hom.: 2836 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.155 AC: 23586 AN: 152218 Hom.: 2849 Cov.: 33 AF XY: 0.168 AC XY: 12533 AN XY: 74414

African (AFR) AF: 0.186 AC: 7713 AN: 41542

American (AMR) AF: 0.223 AC: 3414 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3464

East Asian (EAS) AF: 0.621 AC: 3209 AN: 5168

South Asian (SAS) AF: 0.141 AC: 681 AN: 4826

European-Finnish (FIN) AF: 0.268 AC: 2838 AN: 10586

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5251 AN: 68018

Other (OTH) AF: 0.121 AC: 256 AN: 2112

Alfa AF: 0.0730 Hom.: 140

Bravo AF: 0.157

Asia WGS AF: 0.333 AC: 1162 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.96
CADD	Benign	0.48
DANN	Benign	0.78
PhyloP100		-2.4
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs872010; hg19: chr16-90088787;