rs72664294

Positions:

• chr16-16211782-A-G
• chr16-16211782-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001171.6(ABCC6):​c.662+403T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 152,222 control chromosomes in the GnomAD database, including 115 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 0.035 (115 hom., cov: 30)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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]

LOC105371100 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0354 (5388/152222) while in subpopulation AFR AF= 0.0461 (1915/41510). AF 95% confidence interval is 0.0444. There are 115 homozygotes in gnomad4. There are 2521 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 115 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC6	NM_001171.6	c.662+403T>C		intron_variant		ENST00000205557.12	NP_001162.5
LOC105371100	XR_933131.3	n.89-116A>G		intron_variant, non_coding_transcript_variant
ABCC6	NM_001351800.1	c.320+403T>C		intron_variant			NP_001338729.1
ABCC6	NR_147784.1	n.699+403T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC6	ENST00000205557.12	c.662+403T>C		intron_variant		1	NM_001171.6	ENSP00000205557	P1

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5374 AN: 152104 Hom.: 112 Cov.: 30

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0310

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0354 AC: 5388 AN: 152222 Hom.: 115 Cov.: 30 AF XY: 0.0339 AC XY: 2521 AN XY: 74416

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.0310

Gnomad4 NFE AF: 0.0369

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0378 Hom.: 10

Bravo AF: 0.0357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.81

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: rs72664294; hg19: chr16-16305639;