rs212077

Positions:

• chr16-16186919-G-C

Variant summary

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

The NM_001171.6(ABCC6):​c.1867+205C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,038 control chromosomes in the GnomAD database, including 1,752 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 0.14 (1752 hom., cov: 29)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

ABCC6 (HGNC:57): (ATP binding cassette subfamily C member 6) The 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). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.1867+205C>G		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.1525+205C>G		intron_variant
ABCC6	NR_147784.1	n.1904+205C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.1867+205C>G		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000456970.6	c.1867+205C>G		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.1867+205C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21127 AN: 151920 Hom.: 1754 Cov.: 29

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.139 AC: 21123 AN: 152038 Hom.: 1752 Cov.: 29 AF XY: 0.137 AC XY: 10212 AN XY: 74324

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0543

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.173

Alfa AF: 0.152 Hom.: 234

Bravo AF: 0.135

Asia WGS AF: 0.112 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.67
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs212077; hg19: chr16-16280776;