rs4149338

Variant names:

• chr9-104783622-G-A
• rs4149338
• NM_005502.4:c.*693C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-104783622-G-A
• chr9-104783622-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005502.4(ABCA1):​c.*693C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,270 control chromosomes in the GnomAD database, including 9,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9297 hom., cov: 31)
  • Exomes 𝑓: 0.22 (8 hom.)
• Consequence: ABCA1 NM_005502.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.712
• Publications: 23 publications found

Genes affected

ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

NIPSNAP3B (HGNC:23641): (nipsnap homolog 3B) NIPSNAP3B belongs to a family of proteins with putative roles in vesicular trafficking (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-104783622-G-A is Benign according to our data. Variant chr9-104783622-G-A is described in ClinVar as Benign. ClinVar VariationId is 364361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005502.4. 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
	ABCA1	NM_005502.4	MANE Select	c.*693C>T		3_prime_UTR	Exon 50 of 50	NP_005493.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.*693C>T		3_prime_UTR	Exon 50 of 50	ENSP00000363868.3	O95477
	ABCA1	ENST00000678995.1		c.*693C>T		3_prime_UTR	Exon 50 of 50	ENSP00000504612.1	A0A7I2V5U0

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51078 AN: 151852 Hom.: 9276 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.223 AC: 67 AN: 300 Hom.: 8 Cov.: 0 AF XY: 0.250 AC XY: 47 AN XY: 188

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.231 AC: 6 AN: 26

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 4 AN: 8

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.214 AC: 54 AN: 252

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.337 AC: 51141 AN: 151970 Hom.: 9297 Cov.: 31 AF XY: 0.338 AC XY: 25125 AN XY: 74258

African (AFR) AF: 0.376 AC: 15563 AN: 41440

American (AMR) AF: 0.392 AC: 5981 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3901 AN: 5162

South Asian (SAS) AF: 0.344 AC: 1653 AN: 4806

European-Finnish (FIN) AF: 0.282 AC: 2981 AN: 10578

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19274 AN: 67958

Other (OTH) AF: 0.330 AC: 693 AN: 2100

Alfa AF: 0.308 Hom.: 32984

Bravo AF: 0.350

Asia WGS AF: 0.579 AC: 2011 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypoalphalipoproteinemia, primary, 1 (1)
-	-	1	Tangier disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.65
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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: rs4149338; hg19: chr9-107545903;