16-16195147-A-T

Position:

• chr16-16195147-A-T

Variant summary

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

The NM_001171.6(ABCC6):​c.1339-2225T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 151,814 control chromosomes in the GnomAD database, including 3,873 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 (3873 hom., cov: 31)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC6	NM_001171.6	c.1339-2225T>A		intron_variant		ENST00000205557.12
ABCC6	NM_001351800.1	c.997-2225T>A		intron_variant
ABCC6	NR_147784.1	n.1376-2225T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC6	ENST00000205557.12	c.1339-2225T>A		intron_variant		1	NM_001171.6	P1
ABCC6	ENST00000574094.6	c.1339-332T>A		intron_variant		5
ABCC6	ENST00000456970.6	c.1339-2225T>A		intron_variant, NMD_transcript_variant		2
ABCC6	ENST00000622290.5	c.1339-2225T>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26254 AN: 151696 Hom.: 3854 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.173 AC: 26320 AN: 151814 Hom.: 3873 Cov.: 31 AF XY: 0.181 AC XY: 13397 AN XY: 74186

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0557

Gnomad4 OTH AF: 0.152

Alfa AF: 0.0349 Hom.: 33

Bravo AF: 0.180

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.63

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: rs7192303; hg19: chr16-16289004;