7-87695070-G-A

Position:

• chr7-87695070-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134405.2(RUNDC3B):​c.239-5351G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 152,114 control chromosomes in the GnomAD database, including 264 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.048 (264 hom., cov: 32)
• Consequence: RUNDC3B NM_001134405.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

Genes affected

RUNDC3B (HGNC:30286): (RUN domain containing 3B)

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNDC3B	NM_001134405.2	c.239-5351G>A		intron_variant		ENST00000394654.4	NP_001127877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNDC3B	ENST00000394654.4	c.239-5351G>A		intron_variant		2	NM_001134405.2	ENSP00000378149	P1

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7352 AN: 151996 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.0907

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0512

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

GnomAD4 genome AF: 0.0483 AC: 7350 AN: 152114 Hom.: 264 Cov.: 32 AF XY: 0.0488 AC XY: 3628 AN XY: 74380

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.0901

Gnomad4 SAS AF: 0.0350

Gnomad4 FIN AF: 0.0370

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0314 Hom.: 104

Bravo AF: 0.0529

Asia WGS AF: 0.0580 AC: 200 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs7796247; hg19: chr7-87324386;