1-150560832-C-A

Variant names:

• chr1-150560832-C-A
• rs35531650
• NM_019032.6:c.*636C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_019032.6(ADAMTSL4):​c.*636C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 158,430 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (58 hom., cov: 32)
  • Exomes 𝑓: 0.020 (1 hom.)
• Consequence: ADAMTSL4 NM_019032.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.461
• Publications: 0 publications found

Genes affected

ADAMTSL4 (HGNC:19706): (ADAMTS like 4) This gene is a member of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-like gene family and encodes a protein with seven thrombospondin type 1 repeats. The thrombospondin type 1 repeat domain is found in many proteins with diverse biological functions including cellular adhesion, angiogenesis, and patterning of the developing nervous system. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Sep 2014]

ADAMTSL4-AS1 (HGNC:32041): (ADAMTSL4 antisense RNA 1)

MCL1 (HGNC:6943): (MCL1 apoptosis regulator, BCL2 family member) This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-150560832-C-A is Benign according to our data. Variant chr1-150560832-C-A is described in ClinVar as Benign. ClinVar VariationId is 292576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0211 (3208/152284) while in subpopulation NFE AF = 0.0339 (2309/68014). AF 95% confidence interval is 0.0328. There are 58 homozygotes in GnomAd4. There are 1486 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019032.6. 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
	ADAMTSL4	NM_019032.6	MANE Select	c.*636C>A		3_prime_UTR	Exon 19 of 19	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.*636C>A		3_prime_UTR	Exon 20 of 20	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.*636C>A		3_prime_UTR	Exon 19 of 19	NP_001365525.1	Q6UY14-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.*636C>A		3_prime_UTR	Exon 19 of 19	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000369038.6	TSL:1	c.*636C>A		3_prime_UTR	Exon 17 of 17	ENSP00000358034.2	Q6UY14-1
	ADAMTSL4	ENST00000369039.9	TSL:5	c.*636C>A		3_prime_UTR	Exon 20 of 20	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3210 AN: 152166 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.00874

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00747

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.0203 AC: 125 AN: 6146 Hom.: 1 Cov.: 0 AF XY: 0.0190 AC XY: 67 AN XY: 3526

African (AFR) AF: 0.00 AC: 0 AN: 34

American (AMR) AF: 0.00563 AC: 6 AN: 1066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 38

East Asian (EAS) AF: 0.00 AC: 0 AN: 128

South Asian (SAS) AF: 0.00917 AC: 13 AN: 1418

European-Finnish (FIN) AF: 0.0326 AC: 3 AN: 92

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0313 AC: 98 AN: 3128

Other (OTH) AF: 0.0208 AC: 5 AN: 240

GnomAD4 genome AF: 0.0211 AC: 3208 AN: 152284 Hom.: 58 Cov.: 32 AF XY: 0.0200 AC XY: 1486 AN XY: 74464

African (AFR) AF: 0.00871 AC: 362 AN: 41558

American (AMR) AF: 0.00882 AC: 135 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

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

South Asian (SAS) AF: 0.00726 AC: 35 AN: 4818

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0339 AC: 2309 AN: 68014

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.0290 Hom.: 7

Bravo AF: 0.0195

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ectopia lentis 2, isolated, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.40
DANN	Benign	0.45
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs35531650; hg19: chr1-150533308;