16-16195269-G-C

Position:

• chr16-16195269-G-C

Variant summary

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

The ENST00000205557.12(ABCC6):​c.1339-2347C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 148,216 control chromosomes in the GnomAD database, including 3,821 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 0.17 (3821 hom., cov: 29)
• Consequence: ABCC6 ENST00000205557.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.1339-2347C>G		intron_variant		ENST00000205557.12	NP_001162.5
ABCC6	NM_001351800.1	c.997-2347C>G		intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.1376-2347C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.1339-2347C>G		intron_variant		1	NM_001171.6	ENSP00000205557	P1
ABCC6	ENST00000574094.6	c.1339-454C>G		intron_variant		5		ENSP00000507301
ABCC6	ENST00000456970.6	c.1339-2347C>G		intron_variant, NMD_transcript_variant		2		ENSP00000405002
ABCC6	ENST00000622290.5	c.1339-2347C>G		intron_variant, NMD_transcript_variant		5		ENSP00000483331

Frequencies

GnomAD3 genomes AF: 0.175 AC: 25852 AN: 148112 Hom.: 3802 Cov.: 29

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.0398

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0967

Gnomad NFE AF: 0.0563

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.175 AC: 25918 AN: 148216 Hom.: 3821 Cov.: 29 AF XY: 0.183 AC XY: 13159 AN XY: 72012

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0563

Gnomad4 OTH AF: 0.153

Alfa AF: 0.0912 Hom.: 899

Bravo AF: 0.180

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.41

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: rs7190447; hg19: chr16-16289126;