rs41278170

Variant names:

• chr16-16150322-G-A
• rs41278170
• NM_001171.6:c.4404-81C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001171.6(ABCC6):​c.4404-81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,596,518 control chromosomes in the GnomAD database, including 35 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 0.0041 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (34 hom.)
• Consequence: ABCC6 NM_001171.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 0 publications found

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]

ABCC6 Gene-Disease associations (from GenCC):

• arterial calcification, generalized, of infancy, 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• autosomal recessive inherited pseudoxanthoma elasticum

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine, Orphanet
• inherited pseudoxanthoma elasticum

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00407 (620/152366) while in subpopulation NFE AF = 0.00679 (462/68034). AF 95% confidence interval is 0.00628. There are 1 homozygotes in GnomAd4. There are 288 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 34 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	NM_001171.6	MANE Select	c.4404-81C>T		intron	N/A	NP_001162.5
	ABCC6	NM_001440309.1		c.4371-81C>T		intron	N/A	NP_001427238.1
	ABCC6	NM_001440310.1		c.4236-81C>T		intron	N/A	NP_001427239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC6	ENST00000205557.12	TSL:1 MANE Select	c.4404-81C>T		intron	N/A	ENSP00000205557.7	O95255-1
	ABCC6	ENST00000909083.1		c.4500-81C>T		intron	N/A	ENSP00000579142.1
	ABCC6	ENST00000909090.1		c.4497-81C>T		intron	N/A	ENSP00000579149.1

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 620 AN: 152248 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00679

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00638 AC: 9211 AN: 1444152 Hom.: 34 AF XY: 0.00619 AC XY: 4439 AN XY: 717274

African (AFR) AF: 0.00102 AC: 34 AN: 33172

American (AMR) AF: 0.00260 AC: 107 AN: 41188

Ashkenazi Jewish (ASJ) AF: 0.00194 AC: 50 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 39034

South Asian (SAS) AF: 0.000684 AC: 58 AN: 84846

European-Finnish (FIN) AF: 0.00171 AC: 88 AN: 51586

Middle Eastern (MID) AF: 0.00405 AC: 23 AN: 5684

European-Non Finnish (NFE) AF: 0.00769 AC: 8480 AN: 1103160

Other (OTH) AF: 0.00621 AC: 371 AN: 59706

GnomAD4 genome AF: 0.00407 AC: 620 AN: 152366 Hom.: 1 Cov.: 33 AF XY: 0.00387 AC XY: 288 AN XY: 74504

African (AFR) AF: 0.00166 AC: 69 AN: 41594

American (AMR) AF: 0.00385 AC: 59 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00679 AC: 462 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00461 Hom.: 0

Bravo AF: 0.00424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs41278170; hg19: chr16-16244179;